USP8 Data Analysis

HGNC Gene Name
ubiquitin specific peptidase 8
HGNC Gene Symbol
USP8
Identifiers
hgnc:12631 NCBIGene:9101 uniprot:P40818
Orthologs
mgi:1934029 rgd:1304979
INDRA Statements
deubiquitinations all statements
Pathway Commons
Search for USP8
Number of Papers
289 retrieved on 2023-02-19

DepMap Analysis

The Dependency Map (DepMap) is a genome-wide pooled CRISPR-Cas9 knockout proliferation screen conducted in more than 700 cancer cell lines spanning many different tumor lineages. Each cell line in the DepMap contains a unique barcode, and each gene knockout is assigned a “dependency score” on a per cell-line basis which quantifies the rate of CRISPR-Cas9 guide drop. It has been found that proteins with similar DepMap scores across cell lines, a phenomenon known as co-dependent genes, have closely related biological functions. This can include activity in the same or parallel pathways or membership in the same protein complex or the same pathway.

We identified the strongest seven co-dependent genes (“Symbol”) for DUBs and ran GO enrichment analysis. We used Biogrid, IntAct, and Pathway Commons PPIDs, and the NURSA protein-protein interaction databases (PPIDs) to determine whether co-dependent genes interact with one another. The “Evidence” column contains the PPIDs in which the interaction appears as well as whether there is support for the association by an INDRA statement. As another approach to identify potential interactors, we looked at proteomics data from the Broad Institute's Cancer Cell Line Encyclopedia (CCLE) for proteins whose expression across ~375 cell lines strongly correlated with the abundance of each DUB; it has previously been observed that proteins in the same complex are frequently significantly co-expressed. The correlations and associated p-values in the CCLE proteomics dataset are provided. And, we determined whether co-dependent genes yield similar transcriptomic signatures in the Broad Institute's Connectivity Map (CMap). A CMap score greater than 90 is considered significantly similar.

DepMap Correlations

Symbol Name DepMap Correlation Evidence CCLE Correlation CCLE Z-score CCLE p-value (adj) CCLE Significant CMAP Score CMAP Type
PTPN23 protein tyrosine phosphatase non-receptor type 23 0.563 INDRA (4) 0.50 2.65 8.26e-23
UBAP1 ubiquitin associated protein 1 0.454 0.30 1.57 2.78e-08
HGS hepatocyte growth factor-regulated tyrosine kinase substrate 0.438 INDRA (10) Reactome (8) 0.15 0.72 1.29e-02
STAMBP STAM binding protein 0.377 INDRA (6) Reactome (3) 0.32 1.68 2.51e-09 97.75 kd
CLTC clathrin heavy chain 0.346 Reactome (3) 0.35 1.83 6.25e-11
VPS37A VPS37A subunit of ESCRT-I 0.343 0.37 1.97 1.48e-12
VPS36 vacuolar protein sorting 36 homolog 0.324 0.49 2.60 6.28e-22

Dependency GO Term Enrichment

Gene set enrichment analysis was done on the genes correlated with USP8using the terms from Gene Ontology and gene sets derived from the Gene Ontology Annotations database via MSigDB.

Using the biological processes and other Gene Ontology terms from well characterized DUBs as a positive control, several gene set enrichment analyses were considered. Threshold-less methods like GSEA had relatively poor results. Over-representation analysis with a threshold of of the top 7 highest absolute value Dependency Map correlations yielded the best results and is reported below.

GO Identifier GO Name GO Type p-value p-value (adj.) q-value
GO:0016197 endosomal transport Biological Process 1.62e-11 3.62e-09 1.45e-09
GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway Biological Process 4.73e-11 1.06e-08 2.12e-09
GO:0036452 ESCRT complex Cellular Component 1.13e-10 2.54e-08 3.38e-09
GO:0036257 multivesicular body organization Biological Process 1.38e-07 3.08e-05 3.08e-06
GO:0072666 establishment of protein localization to vacuole Biological Process 4.64e-07 1.04e-04 8.30e-06
GO:0072665 protein localization to vacuole Biological Process 1.15e-06 2.58e-04 1.72e-05
GO:0007032 endosome organization Biological Process 2.40e-06 5.38e-04 3.07e-05
GO:0000813 ESCRT I complex Cellular Component 5.24e-06 1.17e-03 5.86e-05
GO:0031902 late endosome membrane Cellular Component 1.03e-05 2.31e-03 1.02e-04
GO:0007034 vacuolar transport Biological Process 1.29e-05 2.89e-03 1.13e-04
GO:0061919 process utilizing autophagic mechanism Biological Process 1.39e-05 3.11e-03 1.13e-04
GO:0032509 endosome transport via multivesicular body sorting pathway Biological Process 3.21e-05 7.19e-03 2.39e-04
GO:0071985 multivesicular body sorting pathway Biological Process 5.76e-05 1.29e-02 3.96e-04
GO:0006623 protein targeting to vacuole Biological Process 6.90e-05 1.55e-02 4.33e-04
GO:0005770 late endosome Cellular Component 7.25e-05 1.62e-02 4.33e-04
GO:0016236 macroautophagy Biological Process 1.19e-04 2.67e-02 6.68e-04
GO:0016050 vesicle organization Biological Process 1.60e-04 3.58e-02 8.40e-04
GO:0005769 early endosome Cellular Component 1.98e-04 4.43e-02 9.30e-04

Transcriptomics

The following table shows the significantly differentially expressed genes after knocking out USP8 using CRISPR-Cas9.

Knockout Differential Expression

Symbol Name log2-fold-change p-value p-value (adj.)
UBC ubiquitin C 1.04e+00 6.19e-71 3.07e-67
MT1X metallothionein 1X 7.01e-01 1.97e-20 4.89e-17
NAMPT nicotinamide phosphoribosyltransferase 6.54e-01 6.29e-11 1.04e-07
STC1 stanniocalcin 1 7.22e-01 2.65e-09 3.28e-06
MSMO1 methylsterol monooxygenase 1 7.25e-01 1.55e-08 1.54e-05
CD74 CD74 molecule -6.58e-01 4.80e-08 3.54e-05
FTL ferritin light chain 4.07e-01 4.99e-08 3.54e-05
UBB ubiquitin B 2.64e-01 6.06e-08 3.75e-05
HSPA5 heat shock protein family A (Hsp70) member 5 3.75e-01 1.12e-07 6.14e-05
IFIT3 interferon induced protein with tetratricopeptide repeats 3 6.13e-01 2.62e-07 1.30e-04
HMGCS1 3-hydroxy-3-methylglutaryl-CoA synthase 1 7.84e-01 3.22e-07 1.45e-04
BIRC5 baculoviral IAP repeat containing 5 -4.06e-01 5.22e-07 2.04e-04
PGK1 phosphoglycerate kinase 1 3.44e-01 5.34e-07 2.04e-04
GDF15 growth differentiation factor 15 8.81e-01 5.99e-07 2.12e-04
C15orf48 chromosome 15 open reading frame 48 6.20e-01 6.66e-07 2.20e-04
MMP1 matrix metallopeptidase 1 3.63e-01 7.19e-07 2.23e-04
BNIP3 BCL2 interacting protein 3 4.47e-01 8.46e-07 2.30e-04
HMGN2 high mobility group nucleosomal binding domain 2 -3.11e-01 8.11e-07 2.30e-04
SQSTM1 sequestosome 1 5.55e-01 8.83e-07 2.30e-04
CXCL8 C-X-C motif chemokine ligand 8 8.94e-01 9.39e-07 2.33e-04
AKR1C3 aldo-keto reductase family 1 member C3 5.45e-01 1.32e-06 3.12e-04
IFIT1 interferon induced protein with tetratricopeptide repeats 1 8.67e-01 1.44e-06 3.25e-04
INSIG1 insulin induced gene 1 6.74e-01 2.05e-06 4.42e-04
TP53 tumor protein p53 -6.81e-01 2.25e-06 4.64e-04
NDRG1 N-myc downstream regulated 1 7.20e-01 3.88e-06 7.67e-04
TXNRD1 thioredoxin reductase 1 5.40e-01 4.03e-06 7.67e-04
IDI1 isopentenyl-diphosphate delta isomerase 1 4.85e-01 8.97e-06 1.65e-03
CDCA8 cell division cycle associated 8 -5.98e-01 1.02e-05 1.73e-03
FDPS farnesyl diphosphate synthase 3.57e-01 1.05e-05 1.73e-03
HMGA1 high mobility group AT-hook 1 -3.75e-01 1.01e-05 1.73e-03
TNFSF15 TNF superfamily member 15 6.57e-01 1.50e-05 2.40e-03
CD59 CD59 molecule (CD59 blood group) -3.32e-01 2.80e-05 4.33e-03
KLF6 Kruppel like factor 6 3.92e-01 3.09e-05 4.41e-03
RAB13 RAB13, member RAS oncogene family 3.80e-01 3.11e-05 4.41e-03
TUBB4B tubulin beta 4B class IVb -4.04e-01 2.97e-05 4.41e-03
CSF1 colony stimulating factor 1 5.59e-01 3.75e-05 5.15e-03
FDFT1 farnesyl-diphosphate farnesyltransferase 1 5.93e-01 4.70e-05 6.29e-03
SOD2 superoxide dismutase 2 4.25e-01 4.95e-05 6.46e-03
FTH1 ferritin heavy chain 1 4.34e-01 5.68e-05 7.21e-03
HIGD2A HIG1 hypoxia inducible domain family member 2A 3.80e-01 5.82e-05 7.21e-03
NAV3 neuron navigator 3 7.64e-01 6.30e-05 7.62e-03
DNMT1 DNA methyltransferase 1 -3.99e-01 7.07e-05 8.34e-03
IGFBP4 insulin like growth factor binding protein 4 -3.01e-01 8.00e-05 9.19e-03
SKA2 spindle and kinetochore associated complex subunit 2 -4.63e-01 8.16e-05 9.19e-03
HMGA2 high mobility group AT-hook 2 6.27e-01 9.09e-05 1.00e-02
SAT1 spermidine/spermine N1-acetyltransferase 1 4.00e-01 9.34e-05 1.01e-02
RPS28 ribosomal protein S28 7.26e-01 9.76e-05 1.03e-02
CAVIN2 caveolae associated protein 2 -8.39e-01 1.17e-04 1.20e-02
AXL AXL receptor tyrosine kinase -4.59e-01 1.44e-04 1.46e-02
DBI diazepam binding inhibitor, acyl-CoA binding protein 2.49e-01 1.52e-04 1.50e-02
DDX41 DEAD-box helicase 41 5.89e-01 1.55e-04 1.50e-02
IQGAP3 IQ motif containing GTPase activating protein 3 -5.41e-01 1.62e-04 1.54e-02
PLAUR plasminogen activator, urokinase receptor 3.30e-01 1.71e-04 1.60e-02
ERRFI1 ERBB receptor feedback inhibitor 1 4.67e-01 2.20e-04 2.02e-02
HERPUD1 homocysteine inducible ER protein with ubiquitin like domain 1 5.74e-01 2.24e-04 2.02e-02
NAMPTP1 nicotinamide phosphoribosyltransferase pseudogene 1 5.04e-01 2.63e-04 2.33e-02
RPL3P4 ribosomal protein L3 pseudogene 4 6.07e-01 2.90e-04 2.52e-02
PLIN2 perilipin 2 4.28e-01 3.11e-04 2.66e-02
BTG1 BTG anti-proliferation factor 1 5.27e-01 3.30e-04 2.77e-02
SLC7A11 solute carrier family 7 member 11 5.85e-01 3.43e-04 2.83e-02
LRRC75A leucine rich repeat containing 75A -2.90e-01 3.74e-04 3.04e-02
CD44 CD44 molecule (Indian blood group) 3.19e-01 3.89e-04 3.11e-02
NUCKS1 nuclear casein kinase and cyclin dependent kinase substrate 1 -2.83e-01 4.94e-04 3.89e-02
POLR1A RNA polymerase I subunit A -7.11e-01 5.07e-04 3.93e-02
EIF2S3 eukaryotic translation initiation factor 2 subunit gamma -4.20e-01 5.16e-04 3.93e-02
ATP5IF1 ATP synthase inhibitory factor subunit 1 2.33e-01 6.46e-04 4.85e-02
IGFBP7 insulin like growth factor binding protein 7 -3.66e-01 6.77e-04 4.93e-02
NUSAP1 nucleolar and spindle associated protein 1 -3.67e-01 6.69e-04 4.93e-02
AKR1B1 aldo-keto reductase family 1 member B 2.74e-01 6.93e-04 4.98e-02

Gene Set Enrichment Analysis

The GSEA method was applied for all genes whose knockout resulted in at least 20 significantly differentially expressed genes.

ID Name p-value p-value (adj.) log2 Error ES NES
msig:M5925 HALLMARK_E2F_TARGETS 9.51e-20 3.24e-16 1.15e+00 -6.03e-01 -2.68e+00
go:0007049 cell cycle 5.77e-16 9.83e-13 1.03e+00 -3.71e-01 -1.91e+00
go:0005694 chromosome 3.16e-15 3.58e-12 1.01e+00 -4.12e-01 -2.04e+00
reactome:R-HSA-1640170 Cell Cycle 7.03e-15 5.99e-12 9.97e-01 -4.42e-01 -2.15e+00
go:0051301 cell division 1.90e-14 1.29e-11 9.76e-01 -4.74e-01 -2.26e+00
go:0022402 cell cycle process 9.22e-14 5.24e-11 9.55e-01 -3.79e-01 -1.92e+00
reactome:R-HSA-69278 Cell Cycle, Mitotic 2.13e-13 1.04e-10 9.44e-01 -4.49e-01 -2.14e+00
go:0000278 mitotic cell cycle 5.09e-13 2.17e-10 9.21e-01 -3.96e-01 -1.96e+00
msig:M5901 HALLMARK_G2M_CHECKPOINT 1.93e-12 7.29e-10 8.99e-01 -5.45e-01 -2.39e+00
go:0140014 mitotic nuclear division 2.96e-11 1.01e-08 8.51e-01 -5.31e-01 -2.31e+00
go:0000793 condensed chromosome 1.54e-10 4.77e-08 8.27e-01 -5.54e-01 -2.37e+00
go:0007059 chromosome segregation 1.96e-10 5.55e-08 8.27e-01 -5.05e-01 -2.24e+00
go:0051276 chromosome organization 2.52e-10 6.60e-08 8.14e-01 -3.64e-01 -1.82e+00
go:0048285 organelle fission 3.85e-10 9.38e-08 8.14e-01 -4.82e-01 -2.18e+00
msig:M5891 HALLMARK_HYPOXIA 7.72e-10 1.75e-07 8.01e-01 5.68e-01 2.42e+00
msig:M5924 HALLMARK_MTORC1_SIGNALING 2.84e-09 6.04e-07 7.75e-01 4.58e-01 2.10e+00
go:0010564 regulation of cell cycle process 6.80e-09 1.29e-06 7.61e-01 -3.83e-01 -1.86e+00
reactome:R-HSA-69618 Mitotic Spindle Checkpoint 6.77e-09 1.29e-06 7.61e-01 -5.89e-01 -2.33e+00
go:0098813 nuclear chromosome segregation 7.66e-09 1.37e-06 7.48e-01 -5.07e-01 -2.19e+00
reactome:R-HSA-68877 Mitotic Prometaphase 3.19e-08 5.43e-06 7.20e-01 -4.88e-01 -2.12e+00
go:0098687 chromosomal region 4.13e-08 6.70e-06 7.20e-01 -4.43e-01 -2.01e+00
go:0000775 chromosome, centromeric region 4.59e-08 7.11e-06 7.20e-01 -5.11e-01 -2.18e+00
go:0000819 sister chromatid segregation 5.63e-08 8.33e-06 7.20e-01 -5.08e-01 -2.14e+00
reactome:R-HSA-69620 Cell Cycle Checkpoints 9.74e-08 1.38e-05 7.05e-01 -4.40e-01 -1.98e+00
go:0000070 mitotic sister chromatid segregation 1.05e-07 1.43e-05 7.05e-01 -5.48e-01 -2.25e+00
go:0006259 DNA metabolic process 1.15e-07 1.51e-05 7.05e-01 -3.65e-01 -1.78e+00
go:0016126 sterol biosynthetic process 1.47e-07 1.85e-05 6.90e-01 6.90e-01 2.41e+00
reactome:R-HSA-5663220 RHO GTPases Activate Formins 1.52e-07 1.85e-05 6.90e-01 -5.31e-01 -2.16e+00
msig:M7963 KEGG_CELL_CYCLE 1.62e-07 1.91e-05 6.90e-01 -5.83e-01 -2.23e+00
go:0006974 cellular response to DNA damage stimulus 2.00e-07 2.27e-05 6.90e-01 -3.61e-01 -1.75e+00
reactome:R-HSA-2500257 Resolution of Sister Chromatid Cohesion 2.54e-07 2.75e-05 6.75e-01 -5.40e-01 -2.18e+00
go:0008202 steroid metabolic process 2.58e-07 2.75e-05 6.75e-01 5.31e-01 2.22e+00
go:0051726 regulation of cell cycle 2.71e-07 2.80e-05 6.75e-01 -3.30e-01 -1.65e+00
go:1901617 organic hydroxy compound biosynthetic process 3.40e-07 3.40e-05 6.75e-01 5.57e-01 2.26e+00
go:0000776 kinetochore 4.07e-07 3.85e-05 6.75e-01 -5.37e-01 -2.17e+00
go:0006260 DNA replication 4.06e-07 3.85e-05 6.75e-01 -4.66e-01 -2.03e+00
go:0006281 DNA repair 5.03e-07 4.63e-05 6.59e-01 -3.93e-01 -1.85e+00
go:0042175 nuclear outer membrane-endoplasmic reticulum membrane network 5.66e-07 5.07e-05 6.59e-01 3.16e-01 1.66e+00
reactome:R-HSA-556833 Metabolism of lipids 6.20e-07 5.41e-05 6.59e-01 3.79e-01 1.83e+00
go:0006323 DNA packaging 6.43e-07 5.48e-05 6.59e-01 -5.31e-01 -2.14e+00
go:0006694 steroid biosynthetic process 6.88e-07 5.72e-05 6.59e-01 5.77e-01 2.26e+00
go:0005819 spindle 9.75e-07 7.91e-05 6.44e-01 -4.27e-01 -1.92e+00
reactome:R-HSA-8957322 Metabolism of steroids 1.05e-06 8.36e-05 6.44e-01 5.96e-01 2.27e+00
go:0000228 nuclear chromosome 1.25e-06 9.66e-05 6.44e-01 -3.87e-01 -1.82e+00
go:0000779 condensed chromosome, centromeric region 1.54e-06 1.14e-04 6.44e-01 -5.34e-01 -2.11e+00
go:0005773 vacuole 1.54e-06 1.14e-04 6.44e-01 3.52e-01 1.76e+00
go:0006629 lipid metabolic process 2.68e-06 1.94e-04 6.27e-01 3.33e-01 1.70e+00
go:1901615 organic hydroxy compound metabolic process 2.74e-06 1.94e-04 6.27e-01 4.46e-01 1.99e+00
go:0006873 cellular ion homeostasis 2.99e-06 2.07e-04 6.27e-01 4.15e-01 1.91e+00
go:0006261 DNA-dependent DNA replication 3.05e-06 2.07e-04 6.27e-01 -5.25e-01 -2.08e+00
go:0000226 microtubule cytoskeleton organization 3.22e-06 2.15e-04 6.27e-01 -3.93e-01 -1.81e+00
go:0051783 regulation of nuclear division 4.14e-06 2.66e-04 6.11e-01 -4.91e-01 -2.04e+00
go:0034508 centromere complex assembly 4.09e-06 2.66e-04 6.11e-01 -6.96e-01 -2.24e+00
go:0044770 cell cycle phase transition 4.54e-06 2.86e-04 6.11e-01 -3.57e-01 -1.70e+00
reactome:R-HSA-194315 Signaling by Rho GTPases 4.75e-06 2.94e-04 6.11e-01 -4.03e-01 -1.81e+00
go:0002252 immune effector process 5.19e-06 3.16e-04 6.11e-01 3.09e-01 1.63e+00
go:0015630 microtubule cytoskeleton 6.17e-06 3.69e-04 6.11e-01 -3.22e-01 -1.59e+00
go:0046165 alcohol biosynthetic process 6.86e-06 4.03e-04 6.11e-01 5.73e-01 2.21e+00
msig:M5890 HALLMARK_TNFA_SIGNALING_VIA_NFKB 8.01e-06 4.62e-04 5.93e-01 4.87e-01 2.03e+00
go:0006325 chromatin organization 8.49e-06 4.74e-04 5.93e-01 -3.51e-01 -1.68e+00
reactome:R-HSA-68886 M Phase 8.36e-06 4.74e-04 5.93e-01 -3.80e-01 -1.78e+00
msig:M16848 KEGG_EPITHELIAL_CELL_SIGNALING_IN_HELICOBACTER_PYLORI_INFECTION 9.61e-06 5.28e-04 5.93e-01 6.56e-01 2.19e+00
go:0044430 1.14e-05 6.15e-04 5.93e-01 -3.12e-01 -1.56e+00
go:0034097 response to cytokine 1.16e-05 6.20e-04 5.93e-01 2.96e-01 1.55e+00
go:0005783 endoplasmic reticulum 1.33e-05 6.87e-04 5.93e-01 2.67e-01 1.46e+00
reactome:R-HSA-73894 DNA Repair 1.31e-05 6.87e-04 5.93e-01 -4.13e-01 -1.84e+00
reactome:R-HSA-168249 Innate Immune System 1.45e-05 7.37e-04 5.93e-01 3.01e-01 1.57e+00
reactome:R-HSA-195258 RHO GTPase Effectors 1.54e-05 7.71e-04 5.76e-01 -4.12e-01 -1.83e+00
go:0044843 cell cycle G1/S phase transition 1.75e-05 8.53e-04 5.76e-01 -4.48e-01 -1.92e+00
go:0006333 chromatin assembly or disassembly 1.75e-05 8.53e-04 5.76e-01 -5.05e-01 -1.99e+00
msig:M5913 HALLMARK_INTERFERON_GAMMA_RESPONSE 1.83e-05 8.78e-04 5.76e-01 5.06e-01 2.06e+00
msig:M5893 HALLMARK_MITOTIC_SPINDLE 1.88e-05 8.91e-04 5.76e-01 -4.53e-01 -1.91e+00
go:0044437 2.29e-05 1.07e-03 5.76e-01 3.55e-01 1.72e+00
go:0048878 chemical homeostasis 2.32e-05 1.07e-03 5.76e-01 3.20e-01 1.60e+00
go:0007346 regulation of mitotic cell cycle 2.99e-05 1.32e-03 5.76e-01 -3.38e-01 -1.62e+00
go:0000785 chromatin 3.15e-05 1.36e-03 5.57e-01 -3.65e-01 -1.70e+00
go:0050801 ion homeostasis 3.20e-05 1.36e-03 5.57e-01 3.65e-01 1.72e+00
go:0071824 protein-DNA complex subunit organization 3.17e-05 1.36e-03 5.57e-01 -4.27e-01 -1.85e+00
go:0008608 attachment of spindle microtubules to kinetochore 3.39e-05 1.43e-03 5.57e-01 -6.94e-01 -2.17e+00
msig:M11266 KEGG_LYSOSOME 3.81e-05 1.58e-03 5.57e-01 5.50e-01 2.12e+00
go:0034728 nucleosome organization 4.20e-05 1.72e-03 5.57e-01 -5.03e-01 -1.95e+00
reactome:R-HSA-162587 HIV Life Cycle 4.50e-05 1.83e-03 5.57e-01 -4.56e-01 -1.90e+00
go:0055065 metal ion homeostasis 4.82e-05 1.93e-03 5.57e-01 3.81e-01 1.75e+00
go:0002274 myeloid leukocyte activation 5.05e-05 2.00e-03 5.57e-01 3.27e-01 1.62e+00
go:0006952 defense response 5.26e-05 2.06e-03 5.57e-01 2.87e-01 1.52e+00
reactome:R-HSA-191273 Cholesterol biosynthesis 5.46e-05 2.09e-03 5.57e-01 7.66e-01 2.19e+00
reactome:R-HSA-1655829 Regulation of cholesterol biosynthesis by SREBP (SREBF) 5.44e-05 2.09e-03 5.57e-01 6.40e-01 2.14e+00
go:0051983 regulation of chromosome segregation 5.66e-05 2.14e-03 5.57e-01 -5.08e-01 -1.95e+00
reactome:R-HSA-168325 Viral Messenger RNA Synthesis 5.77e-05 2.16e-03 5.57e-01 -6.17e-01 -2.06e+00
reactome:R-HSA-2990846 SUMOylation 6.11e-05 2.26e-03 5.38e-01 -4.63e-01 -1.88e+00
go:0060968 regulation of gene silencing 6.16e-05 2.26e-03 5.38e-01 -4.96e-01 -1.93e+00
go:1901701 cellular response to oxygen-containing compound 6.61e-05 2.40e-03 5.38e-01 3.09e-01 1.59e+00
go:0051290 protein heterotetramerization 7.02e-05 2.52e-03 5.38e-01 -7.32e-01 -2.06e+00
reactome:R-HSA-68962 Activation of the pre-replicative complex 7.12e-05 2.53e-03 5.38e-01 -7.02e-01 -2.06e+00
msig:M5892 HALLMARK_CHOLESTEROL_HOMEOSTASIS 7.42e-05 2.58e-03 5.38e-01 5.82e-01 2.12e+00
go:0018205 peptidyl-lysine modification 7.42e-05 2.58e-03 5.38e-01 -4.09e-01 -1.80e+00
go:0051607 defense response to virus 8.06e-05 2.77e-03 5.38e-01 4.38e-01 1.87e+00
go:0031055 chromatin remodeling at centromere 8.14e-05 2.77e-03 5.38e-01 -6.76e-01 -2.11e+00
reactome:R-HSA-69190 DNA strand elongation 1.09e-04 3.67e-03 5.38e-01 -6.70e-01 -2.09e+00
go:0007010 cytoskeleton organization 1.19e-04 3.97e-03 5.38e-01 -3.07e-01 -1.51e+00
go:0019218 regulation of steroid metabolic process 1.21e-04 3.99e-03 5.38e-01 5.95e-01 2.06e+00
go:1901698 response to nitrogen compound 1.35e-04 4.37e-03 5.19e-01 3.06e-01 1.55e+00
go:0071103 DNA conformation change 1.36e-04 4.37e-03 5.19e-01 -4.04e-01 -1.75e+00
go:0051321 meiotic cell cycle 1.49e-04 4.73e-03 5.19e-01 -4.82e-01 -1.92e+00
go:0008610 lipid biosynthetic process 1.55e-04 4.83e-03 5.19e-01 3.53e-01 1.64e+00
go:0001775 cell activation 1.54e-04 4.83e-03 5.19e-01 2.81e-01 1.49e+00
go:0043486 histone exchange 1.57e-04 4.86e-03 5.19e-01 -6.11e-01 -2.02e+00
reactome:R-HSA-2555396 Mitotic Metaphase and Anaphase 1.60e-04 4.91e-03 5.19e-01 -3.94e-01 -1.73e+00
go:0005125 cytokine activity 1.66e-04 5.06e-03 5.19e-01 5.96e-01 1.99e+00
go:0016925 protein sumoylation 1.72e-04 5.20e-03 5.19e-01 -5.71e-01 -1.97e+00
go:0043044 ATP-dependent chromatin remodeling 1.80e-04 5.39e-03 5.19e-01 -5.37e-01 -1.96e+00
go:0000922 spindle pole 1.91e-04 5.67e-03 5.19e-01 -4.54e-01 -1.83e+00
go:0034724 DNA replication-independent nucleosome organization 1.97e-04 5.72e-03 5.19e-01 -6.03e-01 -2.00e+00
reactome:R-HSA-983231 Factors involved in megakaryocyte development and platelet production 1.97e-04 5.72e-03 5.19e-01 -5.27e-01 -1.96e+00
msig:M5898 HALLMARK_DNA_REPAIR 2.04e-04 5.89e-03 5.19e-01 -4.39e-01 -1.83e+00
go:0090734 site of DNA damage 2.06e-04 5.90e-03 5.19e-01 -5.54e-01 -1.96e+00
go:0006984 ER-nucleus signaling pathway 2.22e-04 6.30e-03 5.19e-01 6.28e-01 2.08e+00
reactome:R-HSA-2426168 Activation of gene expression by SREBF (SREBP) 2.33e-04 6.56e-03 5.19e-01 6.75e-01 2.10e+00
go:0007017 microtubule-based process 2.52e-04 7.00e-03 4.98e-01 -3.30e-01 -1.56e+00
go:0002444 myeloid leukocyte mediated immunity 2.53e-04 7.00e-03 4.98e-01 3.12e-01 1.54e+00
reactome:R-HSA-5693532 DNA Double-Strand Break Repair 2.91e-04 8.01e-03 4.98e-01 -4.69e-01 -1.83e+00
go:0006310 DNA recombination 2.97e-04 8.02e-03 4.98e-01 -4.14e-01 -1.77e+00
reactome:R-HSA-176187 Activation of ATR in response to replication stress 2.96e-04 8.02e-03 4.98e-01 -6.55e-01 -2.01e+00
go:1901700 response to oxygen-containing compound 3.01e-04 8.07e-03 4.98e-01 2.67e-01 1.43e+00
msig:M16853 KEGG_DNA_REPLICATION 3.04e-04 8.09e-03 4.98e-01 -6.26e-01 -1.99e+00
go:0040029 regulation of gene expression, epigenetic 3.19e-04 8.42e-03 4.98e-01 -3.73e-01 -1.66e+00
reactome:R-HSA-73886 Chromosome Maintenance 3.35e-04 8.77e-03 4.98e-01 -5.13e-01 -1.88e+00
go:0045787 positive regulation of cell cycle 3.49e-04 9.01e-03 4.98e-01 -3.68e-01 -1.65e+00
go:0072507 divalent inorganic cation homeostasis 3.53e-04 9.01e-03 4.98e-01 4.23e-01 1.80e+00
go:0031935 regulation of chromatin silencing 3.54e-04 9.01e-03 4.98e-01 -7.17e-01 -1.98e+00
go:0035861 site of double-strand break 3.50e-04 9.01e-03 4.98e-01 -5.72e-01 -1.93e+00
reactome:R-HSA-6796648 TP53 Regulates Transcription of DNA Repair Genes 3.72e-04 9.39e-03 4.98e-01 -5.50e-01 -1.94e+00
go:0050810 regulation of steroid biosynthetic process 3.86e-04 9.66e-03 4.98e-01 5.98e-01 2.02e+00
reactome:R-HSA-159230 Transport of the SLBP Dependant Mature mRNA 3.93e-04 9.78e-03 4.98e-01 -6.44e-01 -2.01e+00
go:0006302 double-strand break repair 4.31e-04 1.06e-02 4.98e-01 -4.28e-01 -1.79e+00
msig:M5908 HALLMARK_ANDROGEN_RESPONSE 4.39e-04 1.07e-02 4.98e-01 4.71e-01 1.84e+00
go:0098542 defense response to other organism 4.65e-04 1.13e-02 4.98e-01 3.81e-01 1.70e+00
go:0019216 regulation of lipid metabolic process 4.82e-04 1.16e-02 4.98e-01 3.91e-01 1.72e+00
msig:M15569 KEGG_NOD_LIKE_RECEPTOR_SIGNALING_PATHWAY 5.00e-04 1.20e-02 4.77e-01 6.90e-01 2.00e+00
go:0090068 positive regulation of cell cycle process 5.05e-04 1.20e-02 4.77e-01 -3.88e-01 -1.68e+00
go:0002682 regulation of immune system process 5.14e-04 1.22e-02 4.77e-01 2.67e-01 1.41e+00
go:0019725 cellular homeostasis 5.49e-04 1.29e-02 4.77e-01 2.99e-01 1.49e+00
go:0044433 5.76e-04 1.34e-02 4.77e-01 2.57e-01 1.38e+00
go:0001786 phosphatidylserine binding 6.02e-04 1.39e-02 4.77e-01 -6.83e-01 -1.92e+00
reactome:R-HSA-1280215 Cytokine Signaling in Immune system 6.12e-04 1.41e-02 4.77e-01 2.96e-01 1.50e+00
go:0005774 vacuolar membrane 6.39e-04 1.45e-02 4.77e-01 3.48e-01 1.61e+00
go:1901681 sulfur compound binding 6.38e-04 1.45e-02 4.77e-01 4.36e-01 1.77e+00
go:0009615 response to virus 6.56e-04 1.48e-02 4.77e-01 3.78e-01 1.69e+00
reactome:R-HSA-69242 S Phase 6.74e-04 1.51e-02 4.77e-01 -4.01e-01 -1.70e+00
go:0009607 response to biotic stimulus 6.79e-04 1.51e-02 4.77e-01 2.97e-01 1.48e+00
go:0000790 chromatin 7.11e-04 1.57e-02 4.77e-01 -3.79e-01 -1.65e+00
msig:M5947 HALLMARK_IL2_STAT5_SIGNALING 7.67e-04 1.68e-02 4.77e-01 4.53e-01 1.83e+00
go:0000794 condensed nuclear chromosome 7.69e-04 1.68e-02 4.77e-01 -5.67e-01 -1.93e+00
go:0031349 positive regulation of defense response 8.22e-04 1.78e-02 4.77e-01 3.46e-01 1.59e+00
reactome:R-HSA-4615885 SUMOylation of DNA replication proteins 8.28e-04 1.79e-02 4.77e-01 -5.61e-01 -1.87e+00
go:1903046 meiotic cell cycle process 8.37e-04 1.79e-02 4.77e-01 -4.78e-01 -1.80e+00
go:0050729 positive regulation of inflammatory response 8.64e-04 1.83e-02 4.77e-01 5.51e-01 1.88e+00
go:0061695 transferase complex, transferring phosphorus-containing groups 9.05e-04 1.90e-02 4.77e-01 -4.00e-01 -1.69e+00
reactome:R-HSA-168898 Toll-like Receptor Cascades 9.17e-04 1.92e-02 4.77e-01 4.95e-01 1.87e+00
reactome:R-HSA-375276 Peptide ligand-binding receptors 9.73e-04 2.02e-02 4.77e-01 6.73e-01 1.95e+00
go:0002221 pattern recognition receptor signaling pathway 9.91e-04 2.05e-02 4.55e-01 4.85e-01 1.87e+00
go:0030141 secretory granule 1.01e-03 2.06e-02 4.55e-01 2.86e-01 1.45e+00
reactome:R-HSA-373076 Class A/1 (Rhodopsin-like receptors) 1.03e-03 2.09e-02 4.55e-01 6.43e-01 2.00e+00
go:0000725 recombinational repair 1.05e-03 2.13e-02 4.55e-01 -4.68e-01 -1.77e+00
reactome:R-HSA-167172 Transcription of the HIV genome 1.06e-03 2.14e-02 4.55e-01 -5.04e-01 -1.79e+00
msig:M5932 HALLMARK_INFLAMMATORY_RESPONSE 1.17e-03 2.35e-02 4.55e-01 4.49e-01 1.76e+00
go:0051298 centrosome duplication 1.19e-03 2.38e-02 4.55e-01 -5.61e-01 -1.86e+00
go:0051235 maintenance of location 1.21e-03 2.39e-02 4.55e-01 3.87e-01 1.67e+00
reactome:R-HSA-6798695 Neutrophil degranulation 1.24e-03 2.42e-02 4.55e-01 3.02e-01 1.46e+00
reactome:R-HSA-168274 Export of Viral Ribonucleoproteins from Nucleus 1.24e-03 2.42e-02 4.55e-01 -6.34e-01 -1.88e+00
go:0051186 1.28e-03 2.49e-02 4.55e-01 3.14e-01 1.49e+00
reactome:R-HSA-4085377 SUMOylation of SUMOylation proteins 1.34e-03 2.59e-02 4.55e-01 -6.10e-01 -1.87e+00
go:0051310 metaphase plate congression 1.42e-03 2.74e-02 4.55e-01 -5.43e-01 -1.81e+00
go:0043621 protein self-association 1.46e-03 2.80e-02 4.55e-01 -6.59e-01 -1.86e+00
go:0055085 transmembrane transport 1.50e-03 2.84e-02 4.55e-01 2.69e-01 1.40e+00
go:0032101 regulation of response to external stimulus 1.50e-03 2.84e-02 4.55e-01 3.16e-01 1.49e+00
go:0042592 homeostatic process 1.52e-03 2.85e-02 4.55e-01 2.52e-01 1.36e+00
go:0099513 polymeric cytoskeletal fiber 1.55e-03 2.89e-02 4.55e-01 -3.31e-01 -1.52e+00
go:0009991 response to extracellular stimulus 1.61e-03 2.99e-02 4.55e-01 3.36e-01 1.54e+00
go:0007292 female gamete generation 1.64e-03 3.03e-02 4.55e-01 -5.52e-01 -1.83e+00
go:0002263 cell activation involved in immune response 1.66e-03 3.06e-02 4.55e-01 2.87e-01 1.43e+00
go:0010469 regulation of signaling receptor activity 1.86e-03 3.38e-02 4.55e-01 3.95e-01 1.68e+00
go:0071453 cellular response to oxygen levels 1.88e-03 3.38e-02 4.55e-01 3.59e-01 1.60e+00
reactome:R-HSA-909733 Interferon alpha/beta signaling 1.87e-03 3.38e-02 4.55e-01 5.88e-01 1.87e+00
go:0019221 cytokine-mediated signaling pathway 1.89e-03 3.38e-02 4.55e-01 2.94e-01 1.44e+00
go:0003682 chromatin binding 1.88e-03 3.38e-02 4.55e-01 -3.28e-01 -1.50e+00
go:0044255 cellular lipid metabolic process 1.93e-03 3.42e-02 4.55e-01 3.08e-01 1.48e+00
go:0009124 nucleoside monophosphate biosynthetic process 2.05e-03 3.62e-02 4.32e-01 -5.52e-01 -1.80e+00
go:0032527 protein exit from endoplasmic reticulum 2.23e-03 3.92e-02 4.32e-01 5.52e-01 1.86e+00
go:0046890 regulation of lipid biosynthetic process 2.24e-03 3.92e-02 4.32e-01 4.39e-01 1.70e+00
go:0018193 peptidyl-amino acid modification 2.26e-03 3.93e-02 4.32e-01 -2.83e-01 -1.38e+00
reactome:R-HSA-176033 Interactions of Vpr with host cellular proteins 2.31e-03 3.96e-02 4.32e-01 -5.81e-01 -1.84e+00
go:0016591 RNA polymerase II, holoenzyme 2.30e-03 3.96e-02 4.32e-01 -4.90e-01 -1.78e+00
go:0048640 negative regulation of developmental growth 2.31e-03 3.96e-02 4.32e-01 5.80e-01 1.85e+00
go:0016705 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen 2.34e-03 3.98e-02 4.32e-01 5.25e-01 1.77e+00
go:0045087 innate immune response 2.35e-03 3.98e-02 4.32e-01 2.89e-01 1.44e+00
go:1901987 regulation of cell cycle phase transition 2.41e-03 4.05e-02 4.32e-01 -3.22e-01 -1.51e+00
go:0005814 centriole 2.45e-03 4.06e-02 4.32e-01 -4.65e-01 -1.72e+00
go:0071384 cellular response to corticosteroid stimulus 2.44e-03 4.06e-02 4.32e-01 5.57e-01 1.86e+00
go:0051304 chromosome separation 2.47e-03 4.09e-02 4.32e-01 -4.89e-01 -1.77e+00
reactome:R-HSA-2980766 Nuclear Envelope Breakdown 2.51e-03 4.09e-02 4.32e-01 -5.27e-01 -1.80e+00
go:0044786 cell cycle DNA replication 2.52e-03 4.09e-02 4.32e-01 -5.06e-01 -1.75e+00
go:0012506 vesicle membrane 2.52e-03 4.09e-02 4.32e-01 2.95e-01 1.46e+00
go:0010948 negative regulation of cell cycle process 2.54e-03 4.11e-02 4.32e-01 -3.42e-01 -1.54e+00
go:0050662 2.62e-03 4.21e-02 4.32e-01 3.68e-01 1.59e+00
go:0044706 multi-multicellular organism process 2.65e-03 4.24e-02 4.32e-01 4.46e-01 1.74e+00
go:0003697 single-stranded DNA binding 2.71e-03 4.31e-02 4.32e-01 -4.57e-01 -1.71e+00
go:0070848 response to growth factor 2.73e-03 4.32e-02 4.32e-01 2.93e-01 1.43e+00
go:0016301 kinase activity 2.77e-03 4.34e-02 4.32e-01 -3.30e-01 -1.51e+00
go:0007584 response to nutrient 2.77e-03 4.34e-02 4.32e-01 4.33e-01 1.74e+00
go:0002443 leukocyte mediated immunity 2.78e-03 4.34e-02 4.32e-01 2.73e-01 1.37e+00
reactome:R-HSA-69473 G2/M DNA damage checkpoint 2.81e-03 4.36e-02 4.32e-01 -5.02e-01 -1.77e+00
go:0005875 microtubule associated complex 2.81e-03 4.36e-02 4.32e-01 -4.54e-01 -1.70e+00
go:1901699 cellular response to nitrogen compound 2.84e-03 4.37e-02 4.32e-01 3.09e-01 1.47e+00
go:0018394 peptidyl-lysine acetylation 2.95e-03 4.52e-02 4.32e-01 -4.51e-01 -1.70e+00
go:0007080 mitotic metaphase plate congression 3.02e-03 4.62e-02 4.32e-01 -5.75e-01 -1.82e+00
go:0051129 negative regulation of cellular component organization 3.08e-03 4.67e-02 4.32e-01 -3.16e-01 -1.48e+00
go:0002753 cytoplasmic pattern recognition receptor signaling pathway 3.07e-03 4.67e-02 4.32e-01 5.51e-01 1.79e+00
reactome:R-HSA-4551638 SUMOylation of chromatin organization proteins 3.13e-03 4.71e-02 4.32e-01 -5.16e-01 -1.74e+00
msig:M5938 HALLMARK_REACTIVE_OXYGEN_SPECIES_PATHWAY 3.14e-03 4.72e-02 4.32e-01 5.10e-01 1.77e+00
reactome:R-HSA-449147 Signaling by Interleukins 3.18e-03 4.75e-02 4.32e-01 2.93e-01 1.40e+00
reactome:R-HSA-917937 Iron uptake and transport 3.19e-03 4.75e-02 4.32e-01 5.19e-01 1.73e+00
reactome:R-HSA-72086 mRNA Capping 3.25e-03 4.81e-02 4.32e-01 -5.72e-01 -1.82e+00
go:0005815 microtubule organizing center 3.26e-03 4.81e-02 4.32e-01 -3.01e-01 -1.43e+00
msig:M5937 HALLMARK_GLYCOLYSIS 3.31e-03 4.84e-02 4.32e-01 3.65e-01 1.57e+00
reactome:R-HSA-5693538 Homology Directed Repair 3.34e-03 4.86e-02 4.32e-01 -4.53e-01 -1.70e+00
go:0045540 regulation of cholesterol biosynthetic process 3.45e-03 5.00e-02 4.32e-01 6.17e-01 1.90e+00
go:0031347 regulation of defense response 3.49e-03 5.03e-02 4.32e-01 3.00e-01 1.44e+00
go:0030496 midbody 3.55e-03 5.11e-02 4.32e-01 -3.89e-01 -1.62e+00
go:1990234 transferase complex 3.59e-03 5.13e-02 4.32e-01 -2.83e-01 -1.37e+00
go:0005768 endosome 3.66e-03 5.19e-02 4.32e-01 2.73e-01 1.37e+00
go:0051302 regulation of cell division 3.69e-03 5.22e-02 4.32e-01 -4.47e-01 -1.68e+00
reactome:R-HSA-3108214 SUMOylation of DNA damage response and repair proteins 3.75e-03 5.25e-02 4.32e-01 -4.76e-01 -1.69e+00
go:0070997 neuron death 3.75e-03 5.25e-02 4.32e-01 3.50e-01 1.55e+00
go:0043902 positive regulation of multi-organism process 3.76e-03 5.25e-02 4.32e-01 -3.96e-01 -1.61e+00
go:0014070 response to organic cyclic compound 3.79e-03 5.27e-02 4.32e-01 2.70e-01 1.36e+00
go:0002224 toll-like receptor signaling pathway 3.88e-03 5.34e-02 4.32e-01 4.99e-01 1.77e+00
go:0034504 protein localization to nucleus 3.87e-03 5.34e-02 4.32e-01 -3.63e-01 -1.55e+00
reactome:R-HSA-159234 Transport of Mature mRNAs Derived from Intronless Transcripts 3.95e-03 5.38e-02 4.07e-01 -5.72e-01 -1.81e+00
go:0007051 spindle organization 3.96e-03 5.38e-02 4.07e-01 -3.95e-01 -1.62e+00
go:0005876 spindle microtubule 3.93e-03 5.38e-02 4.07e-01 -5.30e-01 -1.81e+00
reactome:R-HSA-177243 Interactions of Rev with host cellular proteins 4.04e-03 5.45e-02 4.07e-01 -5.66e-01 -1.80e+00
msig:M15798 KEGG_MELANOMA 4.05e-03 5.45e-02 4.07e-01 -5.94e-01 -1.76e+00
go:0036260 RNA capping 4.27e-03 5.65e-02 4.07e-01 -5.54e-01 -1.79e+00
go:0005657 replication fork 4.26e-03 5.65e-02 4.07e-01 -5.00e-01 -1.76e+00
go:0016772 transferase activity, transferring phosphorus-containing groups 4.24e-03 5.65e-02 4.07e-01 -3.08e-01 -1.46e+00
msig:M9809 KEGG_CYTOKINE_CYTOKINE_RECEPTOR_INTERACTION 4.28e-03 5.65e-02 4.07e-01 5.07e-01 1.75e+00
go:0099503 secretory vesicle 4.32e-03 5.66e-02 4.07e-01 2.69e-01 1.38e+00
go:0097110 scaffold protein binding 4.36e-03 5.69e-02 4.07e-01 -5.92e-01 -1.76e+00
go:0030545 receptor regulator activity 4.44e-03 5.77e-02 4.07e-01 3.88e-01 1.60e+00
msig:M15913 KEGG_RIG_I_LIKE_RECEPTOR_SIGNALING_PATHWAY 4.58e-03 5.91e-02 4.07e-01 6.55e-01 1.87e+00
go:0005506 iron ion binding 4.58e-03 5.91e-02 4.07e-01 5.10e-01 1.70e+00
reactome:R-HSA-382551 Transport of small molecules 4.63e-03 5.91e-02 4.07e-01 3.02e-01 1.43e+00
go:0080134 regulation of response to stress 4.65e-03 5.92e-02 4.07e-01 2.44e-01 1.31e+00
go:0007276 gamete generation 4.70e-03 5.94e-02 4.07e-01 -3.44e-01 -1.52e+00
go:1902930 regulation of alcohol biosynthetic process 4.73e-03 5.97e-02 4.07e-01 5.82e-01 1.82e+00
go:0031023 microtubule organizing center organization 4.88e-03 6.11e-02 4.07e-01 -4.21e-01 -1.61e+00
go:1904949 ATPase complex 4.88e-03 6.11e-02 4.07e-01 -4.54e-01 -1.66e+00
go:0000281 mitotic cytokinesis 4.97e-03 6.18e-02 4.07e-01 -4.96e-01 -1.74e+00
go:1903513 endoplasmic reticulum to cytosol transport 5.05e-03 6.23e-02 4.07e-01 6.03e-01 1.87e+00
go:0006270 DNA replication initiation 5.08e-03 6.23e-02 4.07e-01 -5.99e-01 -1.73e+00
reactome:R-HSA-6803529 FGFR2 alternative splicing 5.09e-03 6.23e-02 4.07e-01 -5.77e-01 -1.77e+00
reactome:R-HSA-73762 RNA Polymerase I Transcription Initiation 5.05e-03 6.23e-02 4.07e-01 -5.22e-01 -1.73e+00
go:0002684 positive regulation of immune system process 5.12e-03 6.25e-02 4.07e-01 2.63e-01 1.33e+00
go:0045177 apical part of cell 5.21e-03 6.29e-02 4.07e-01 3.86e-01 1.61e+00
reactome:R-HSA-5633007 Regulation of TP53 Activity 5.23e-03 6.29e-02 4.07e-01 -3.99e-01 -1.59e+00
msig:M18937 KEGG_NUCLEOTIDE_EXCISION_REPAIR 5.24e-03 6.29e-02 4.07e-01 -5.20e-01 -1.72e+00
go:0051984 positive regulation of chromosome segregation 5.24e-03 6.29e-02 4.07e-01 -5.87e-01 -1.74e+00
go:0045814 negative regulation of gene expression, epigenetic 5.30e-03 6.32e-02 4.07e-01 -4.48e-01 -1.66e+00
go:0071559 response to transforming growth factor beta 5.31e-03 6.32e-02 4.07e-01 3.70e-01 1.55e+00
go:0006915 apoptotic process 5.42e-03 6.42e-02 4.07e-01 2.28e-01 1.26e+00
reactome:R-HSA-3301854 Nuclear Pore Complex (NPC) Disassembly 5.43e-03 6.42e-02 4.07e-01 -5.68e-01 -1.78e+00
go:0008306 associative learning 5.57e-03 6.56e-02 4.07e-01 6.25e-01 1.81e+00
go:0097194 execution phase of apoptosis 5.65e-03 6.62e-02 4.07e-01 -4.77e-01 -1.64e+00
go:0044450 5.64e-03 6.62e-02 4.07e-01 -4.13e-01 -1.61e+00
go:0060548 negative regulation of cell death 5.80e-03 6.76e-02 4.07e-01 2.50e-01 1.30e+00
go:0002039 p53 binding 6.14e-03 7.11e-02 4.07e-01 -5.23e-01 -1.71e+00
go:1901796 regulation of signal transduction by p53 class mediator 6.19e-03 7.15e-02 4.07e-01 -4.00e-01 -1.64e+00
reactome:R-HSA-5578749 Transcriptional regulation by small RNAs 6.23e-03 7.15e-02 4.07e-01 -4.60e-01 -1.64e+00
go:1990841 promoter-specific chromatin binding 6.23e-03 7.15e-02 4.07e-01 -6.16e-01 -1.74e+00
go:0045786 negative regulation of cell cycle 6.30e-03 7.18e-02 4.07e-01 -2.95e-01 -1.40e+00
go:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress 6.29e-03 7.18e-02 4.07e-01 5.38e-01 1.78e+00
go:0071396 cellular response to lipid 6.33e-03 7.18e-02 4.07e-01 3.00e-01 1.41e+00
go:0005643 nuclear pore 6.35e-03 7.19e-02 4.07e-01 -4.70e-01 -1.67e+00
reactome:R-HSA-69306 DNA Replication 6.39e-03 7.20e-02 4.07e-01 -3.81e-01 -1.57e+00
go:0010332 response to gamma radiation 6.42e-03 7.22e-02 4.07e-01 -5.61e-01 -1.77e+00
reactome:R-HSA-936440 Negative regulators of DDX58/IFIH1 signaling 6.53e-03 7.32e-02 4.07e-01 5.94e-01 1.82e+00
go:0031491 nucleosome binding 6.76e-03 7.55e-02 4.07e-01 -4.60e-01 -1.65e+00
reactome:R-HSA-180746 Nuclear import of Rev protein 6.84e-03 7.61e-02 4.07e-01 -5.67e-01 -1.74e+00
go:0051208 sequestering of calcium ion 6.95e-03 7.71e-02 4.07e-01 5.76e-01 1.80e+00
go:0006826 iron ion transport 7.13e-03 7.74e-02 4.07e-01 5.42e-01 1.72e+00
reactome:R-HSA-1839126 FGFR2 mutant receptor activation 7.18e-03 7.74e-02 4.07e-01 -6.09e-01 -1.74e+00
go:0033044 regulation of chromosome organization 7.13e-03 7.74e-02 4.07e-01 -3.30e-01 -1.48e+00
go:0016491 oxidoreductase activity 7.18e-03 7.74e-02 4.07e-01 2.56e-01 1.30e+00
go:0033273 response to vitamin 7.04e-03 7.74e-02 4.07e-01 5.29e-01 1.72e+00
go:0097191 extrinsic apoptotic signaling pathway 7.17e-03 7.74e-02 4.07e-01 -3.83e-01 -1.56e+00
go:0001816 cytokine production 7.15e-03 7.74e-02 4.07e-01 2.95e-01 1.40e+00
go:0032103 positive regulation of response to external stimulus 7.05e-03 7.74e-02 4.07e-01 3.78e-01 1.57e+00
msig:M5109 KEGG_PYRIMIDINE_METABOLISM 7.13e-03 7.74e-02 4.07e-01 -4.29e-01 -1.61e+00
go:0070482 response to oxygen levels 7.21e-03 7.75e-02 4.07e-01 2.99e-01 1.41e+00
msig:M5945 HALLMARK_HEME_METABOLISM 7.28e-03 7.77e-02 4.07e-01 3.64e-01 1.54e+00
go:0002764 immune response-regulating signaling pathway 7.27e-03 7.77e-02 4.07e-01 3.06e-01 1.42e+00
go:0045111 intermediate filament cytoskeleton 7.50e-03 7.99e-02 4.07e-01 -4.80e-01 -1.69e+00
go:0005794 Golgi apparatus 7.59e-03 8.06e-02 4.07e-01 2.36e-01 1.26e+00
go:0071407 cellular response to organic cyclic compound 7.70e-03 8.12e-02 4.07e-01 2.98e-01 1.40e+00
go:0002573 myeloid leukocyte differentiation 7.70e-03 8.12e-02 4.07e-01 4.00e-01 1.57e+00
go:0006812 cation transport 7.73e-03 8.12e-02 4.07e-01 2.75e-01 1.35e+00
go:1900117 regulation of execution phase of apoptosis 7.77e-03 8.14e-02 4.07e-01 -6.08e-01 -1.71e+00
go:0032154 cleavage furrow 8.03e-03 8.39e-02 3.81e-01 -5.14e-01 -1.68e+00
go:0006885 regulation of pH 8.09e-03 8.42e-02 3.81e-01 4.88e-01 1.63e+00
go:0048585 negative regulation of response to stimulus 8.11e-03 8.42e-02 3.81e-01 2.39e-01 1.28e+00
go:1905818 regulation of chromosome separation 8.22e-03 8.48e-02 3.81e-01 -4.69e-01 -1.62e+00
reactome:R-HSA-73933 Resolution of Abasic Sites (AP sites) 8.21e-03 8.48e-02 3.81e-01 -5.53e-01 -1.74e+00
go:0030001 metal ion transport 8.28e-03 8.52e-02 3.81e-01 3.03e-01 1.41e+00
go:0006289 nucleotide-excision repair 8.32e-03 8.53e-02 3.81e-01 -4.09e-01 -1.56e+00
go:0030554 adenyl nucleotide binding 8.34e-03 8.53e-02 3.81e-01 -2.62e-01 -1.30e+00
msig:M5906 HALLMARK_ESTROGEN_RESPONSE_EARLY 8.51e-03 8.60e-02 3.81e-01 3.99e-01 1.56e+00
go:0061982 meiosis I cell cycle process 8.44e-03 8.60e-02 3.81e-01 -4.90e-01 -1.65e+00
go:0005770 late endosome 8.50e-03 8.60e-02 3.81e-01 3.45e-01 1.48e+00
go:0070603 SWI/SNF superfamily-type complex 8.49e-03 8.60e-02 3.81e-01 -4.57e-01 -1.63e+00
reactome:R-HSA-113418 Formation of the Early Elongation Complex 8.57e-03 8.63e-02 3.81e-01 -5.36e-01 -1.73e+00
reactome:R-HSA-168928 DDX58/IFIH1-mediated induction of interferon-alpha/beta 8.68e-03 8.70e-02 3.81e-01 5.09e-01 1.71e+00
reactome:R-HSA-983189 Kinesins 8.72e-03 8.71e-02 3.81e-01 -5.58e-01 -1.71e+00
go:0050000 chromosome localization 8.83e-03 8.80e-02 3.81e-01 -4.74e-01 -1.67e+00
go:0030968 endoplasmic reticulum unfolded protein response 8.87e-03 8.80e-02 3.81e-01 3.97e-01 1.56e+00
go:0021510 spinal cord development 9.07e-03 8.96e-02 3.81e-01 -5.81e-01 -1.71e+00
go:0007062 sister chromatid cohesion 9.07e-03 8.96e-02 3.81e-01 -4.84e-01 -1.66e+00
reactome:R-HSA-983712 Ion channel transport 9.25e-03 9.06e-02 3.81e-01 4.79e-01 1.69e+00
go:0051784 negative regulation of nuclear division 9.28e-03 9.06e-02 3.81e-01 -5.05e-01 -1.67e+00
go:0000075 cell cycle checkpoint 9.26e-03 9.06e-02 3.81e-01 -3.57e-01 -1.51e+00
go:0006665 sphingolipid metabolic process 9.42e-03 9.17e-02 3.81e-01 5.23e-01 1.73e+00
reactome:R-HSA-9614085 FOXO-mediated transcription 9.51e-03 9.23e-02 3.81e-01 5.06e-01 1.71e+00
reactome:R-HSA-168638 NOD1/2 Signaling Pathway 9.55e-03 9.24e-02 3.81e-01 6.30e-01 1.80e+00
go:0033218 amide binding 9.66e-03 9.27e-02 3.81e-01 3.55e-01 1.53e+00
go:0045935 positive regulation of nucleobase-containing compound metabolic process 9.65e-03 9.27e-02 3.81e-01 -3.53e-01 -1.50e+00
go:0043543 protein acylation 9.62e-03 9.27e-02 3.81e-01 -3.79e-01 -1.53e+00
go:0007093 mitotic cell cycle checkpoint 9.80e-03 9.35e-02 3.81e-01 -3.75e-01 -1.52e+00
go:1902850 microtubule cytoskeleton organization involved in mitosis 9.85e-03 9.35e-02 3.81e-01 -4.07e-01 -1.56e+00
msig:M8104 KEGG_AMINO_SUGAR_AND_NUCLEOTIDE_SUGAR_METABOLISM 9.80e-03 9.35e-02 3.81e-01 5.13e-01 1.66e+00
go:0033043 regulation of organelle organization 9.83e-03 9.35e-02 3.81e-01 -2.60e-01 -1.29e+00
go:0010941 regulation of cell death 1.00e-02 9.48e-02 3.81e-01 2.29e-01 1.25e+00
go:1901989 positive regulation of cell cycle phase transition 1.01e-02 9.49e-02 3.81e-01 -4.46e-01 -1.59e+00
go:0022853 active ion transmembrane transporter activity 1.01e-02 9.49e-02 3.81e-01 4.82e-01 1.63e+00
reactome:R-HSA-5696398 Nucleotide Excision Repair 1.01e-02 9.49e-02 3.81e-01 -3.87e-01 -1.53e+00
reactome:R-HSA-1226099 Signaling by FGFR in disease 1.02e-02 9.58e-02 3.81e-01 -5.38e-01 -1.71e+00
go:0032886 regulation of microtubule-based process 1.04e-02 9.68e-02 3.81e-01 -3.74e-01 -1.52e+00
go:0099080 supramolecular complex 1.04e-02 9.68e-02 3.81e-01 -2.94e-01 -1.39e+00
reactome:R-HSA-167287 HIV elongation arrest and recovery 1.05e-02 9.77e-02 3.81e-01 -5.43e-01 -1.70e+00
go:1903573 negative regulation of response to endoplasmic reticulum stress 1.06e-02 9.77e-02 3.81e-01 5.24e-01 1.67e+00
go:0043620 regulation of DNA-templated transcription in response to stress 1.06e-02 9.77e-02 3.81e-01 3.76e-01 1.56e+00
go:0090382 phagosome maturation 1.06e-02 9.77e-02 3.81e-01 6.27e-01 1.79e+00
reactome:R-HSA-199992 trans-Golgi Network Vesicle Budding 1.07e-02 9.78e-02 3.81e-01 4.39e-01 1.63e+00
go:0006970 response to osmotic stress 1.07e-02 9.80e-02 3.81e-01 5.09e-01 1.71e+00
go:0051480 regulation of cytosolic calcium ion concentration 1.09e-02 9.94e-02 3.81e-01 4.26e-01 1.62e+00
go:0048524 positive regulation of viral process 1.09e-02 9.94e-02 3.81e-01 -4.00e-01 -1.54e+00
go:0043628 ncRNA 3'-end processing 1.10e-02 9.94e-02 3.81e-01 -5.52e-01 -1.68e+00
go:0015078 proton transmembrane transporter activity 1.10e-02 9.94e-02 3.81e-01 3.99e-01 1.55e+00
reactome:R-HSA-177929 Signaling by EGFR 1.10e-02 9.94e-02 3.81e-01 5.68e-01 1.76e+00
go:0045071 negative regulation of viral genome replication 1.10e-02 9.94e-02 3.81e-01 5.17e-01 1.71e+00

Literature Mining

INDRA was used to automatically assemble known mechanisms related to USP8 from literature and knowledge bases. The first section shows only DUB activity and the second shows all other results.

Deubiquitinase Activity

psp cbn pc bel_lc signor biogrid tas hprd trrust ctd vhn pe drugbank omnipath conib crog dgi minerva creeds ubibrowser acsn | geneways tees gnbr semrep isi trips rlimsp medscan eidos sparser reach
USP8 deubiquitinates SMO. 10 / 14
1 | 13
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In addition, it has been reported that the deubiquitinase Usp8 could deubiquitinate Smo to influence Hh signaling activity.
26120032
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Although our observations support the notion that USP8 deubiquitinates Smo and prevents localization to early endosomes, we are not suggesting that USP8 play an exclusive role in the inhibition of Smo endocytosis.
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As shown in XREF_FIG, USP8, but not the other DUBs, reduced the ubiquitination of Myc-Smo.
22253573
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Using an in vivo RNAi screen, we identified ubiquitin specific protease 8 (USP8) as a deubiquitinase that down-regulates Smo ubiquitination.
22253573
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Review
27775833
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In addition, it has been reported that the deubiquitinase Usp8 could deubiquitinate Smo to influence Hh signaling activity (Li et al., 2012; Xia et al., 2012).
26120032
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In addition, we provide evidence that the non visual beta-arrestin Krz acts in parallel with Smo ubiquitination to promote its internalization and that Smo ubiquitination is antagonized by the deubiquitinating enzyme UBPY.
22253574
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However, we found that UBPY decreases Smo ubiquitination regardless of the Hh signaling states and that the association between UBPY and Smo is not significantly affected by either Hh stimulation or Smo phosphorylation, suggesting that Smo deubiquitination by UBPY is unlikely to be a major mechanism by which Hh inhibits Smo ubiquitination, although we can not rule out the possibility that Hh regulates UBPY binding to Smo in a subtle way that escaped the detection by our coimmunoprecipitation assay.
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Taken together, these results suggest that UBPY can reverse Smo ubiquitination to promote its cell surface accumulation and induce low but not high levels of Hh pathway activation.
22253574
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Hh promotes the formation of a Smo and USP8 complex, and USP8 further promotes the accumulation of Smo at the cell surface and prevents localization to the early endosomes by deubiquitinating Smo, leading to increased Hh signaling activity.
26973699
USP8 deubiquitinates EGFR. 10 / 13
1 | 1 11
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In an elegant and comprehensive analysis of corticotroph adenoma, Reincke et al demonstrated that heterozygous somatic USP8 single nucleotide mutation or deletions at or adjacent to the 14-3-3 protein binding domain make USP8 resistant to 14-3-3 protein binding and more prone to proteolytic cleavage, which, in turn, leads to higher rate of USP8 induced EGFR deubiquitination activity upon binding of EGF to its receptor.
28520590
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USP8 (also known as UBPY) deubiquitylates EGFR on early endosomes, rescuing EGFR from degradation 107, 108 .
28959952
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Before incorporation into MVBs, the EGFR is deubiquitinated by Usp8.
23333852
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However, we can not fully exclude the other possibility that the UBPY S680A expression resulted in a reduction in the cellular Ub conjugating activity toward activated EGFR in some way.The fact that U[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
17720156
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Based on these studies, we propose a model whereby the concerted recruitment of CHMP4B and UBPY to HD-PTP and the engagement of UBPY by STAM2 displaces ESCRT-0 from HD-PTP, deubiquitinates EGFR, and releases ESCRT-0 from cargo in favor of ESCRT-III.
23477725
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Some studies showed that AMSH [31] and UBPY [32, 33] prevent EGFR down-regulation by deubiquitinating EGFR.
29981430
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While AMSH is required for sorting of EGFR into MVEs and degradation in lysosomes XREF_BIBR, deubiquitination of EGFR by USP8 protects it from lysosomal degradation XREF_BIBR.
23049745
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If USP8 deubiquitylates EGFR at the MVB, this facilitates EGFR 's progression toward degradation in the lysosome and, thus, aids receptor down-regulation.
16702236
ubibrowser
Review
27775833
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Furthermore we demonstrated that both EGFR and EGFR-ErbB2 TM are deubiquitinated by the deubiquitination enzyme Usp8, although deubiquitination of ErbB2 was less efficient than that of EGFR [10].
22800866
USP8 deubiquitinates CHMP1B. 7 / 7
1 | 6
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Thus, deubiquitination of CHMP1B by USP8 at the endosomal membrane may favor CHMP1B oligomerization and co-assembly with IST1 in vivo.
29933386
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Furthermore, we have demonstrated that USP8 deubiquitinates CHMP1B.
29933386
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From these observations, we propose that CHMP1B is dynamically regulated by ubiquitination in response to EGF and that USP8 triggers CHMP1B deubiquitination possibly favoring its subsequent assembly into a membrane associated ESCRT-III polymer.
29933386
ubibrowser
We demonstrate further that CHMP1B is deubiquitinated by the ubiquitin specific protease USP8 (syn. UBPY)
29933386
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Based on these observations, we propose that CHMP1B is dynamically regulated by ubiquitination in response to EGF and that USP8 triggers CHMP1B deubiquitination possibly favoring its subsequent assembly into a membrane associated ESCRT-III polymer.
29933386
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Our results thus strongly suggest that USP8 deubiquitinates CHMP1B.
29933386
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Finally, we observed that the ubiquitination level of endogenous CHMP1B was higher in partially Usp8 silenced cells compared to control cells, strengthening the hypothesis that USP8 deubiquitinates CHMP1B (XREF_FIG).
29933386
USP8 deubiquitinates PRKN. 6 / 6
1 | 5
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Finally, deubiquitination of Parkin by USP8 is required for Parkin recruitment to CCCP intoxicated mitochondria and to promote stress induced mitophagy in vitro.
30988163
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Our findings suggested that H 2 S promoted mitophagy formation by increasing S sulfhydration of USP8, which enhanced deubiquitination of parkin through the recruitment of parkin in mitochondria.
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This process is negatively regulated by USP15 [XREF_BIBR] and USP30 [XREF_BIBR], which deubiquitinate mitochondrial Parkin-targets, while it is supported by USP8, which deubiquitinates Parkin itself [XREF_BIBR].
25545884
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USP8 deubiquitylation of auto-ubiquitylated Parkin is required for its localization to depolarized mitochondria, and thereby for efficient activation of mitophagy [XREF_BIBR].
26611876
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Whilst the phosphatase that dephosphorylates p-Ub remains unknown, two DUBs have been identified that deubiquitylate Parkin directed substrates, USP30 and USP15, and USP8 has also been reported to reverse Parkin autoubiquitylation.
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ubibrowser
USP8 regulates mitophagy by removing K6-linked ubiquitin conjugates from parkin.
25216678
USP8 deubiquitinates CLOCK. 5 / 5
| 5
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As USP8 interacts with CLK and expression of USP8-DN increases CLK ubiquitylation, the data indicate that USP8 deubiquitylates CLK, which down-regulates CLK and CYC transcriptional activity.
23154984
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Since deubiquitylation of CLK by USP8 decreases its activity XREF_BIBR, it will be interesting to investigate whether CK2alpha phosphorylation affects CLK ubiquitylation.
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CLK deubiquitylation by USP8 reinforces transcriptional repression by PER complexes, whereas CLK ubiquitylation and decreased phosphorylation may be involved in shifting CLK to a transcriptionally active state.
23731779
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This rhythm in ubiquitylation is mediated by UBIQUITIN SPECIFIC PROTEASE 8 (USP8), which deubiquitylates CLK to downregulate CLK-CYC activity from ~ ZT18-ZT4, thereby reinforcing PER dependent repression [XREF_BIBR].
23731779
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CLOCK deubiquitylation by USP8 inhibits CLK and CYC transcription in Drosophila.
23154984
USP8 deubiquitinates SQSTM1. 4 / 4
| 4
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USP8 directly deubiquitinates SQSTM1 and p62 and blocks autophagy [XREF_BIBR].
33628391
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USP8 directly deubiquitinates SQSTM1 and p62 and blocks autophagy [XREF_BIBR].
33628391
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USP8 induces the deubiquitination of TRAF6, TAB2, TAK1, p62, and BECN1, which are pivotal roles for NF-κB activation and autophagy induction.
34688043
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USP8 overexpression leads to deubiquitination of p62 protein, suppressing its autophagic activity (Peng et al. 2020).
34689261
USP8 deubiquitinates HGS. 4 / 4
| 4
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We provide evidence that Ubpy interacts with and deubiquitylates Hrs.
24574010
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Mop recruits Ubpy to promote the deubiquitination of Hrs.
26224310
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Studies have shown that USP8 also interacts with and deubiquitinate Hrs, demonstrating multiple roles of USP8 in both cargo de-ubiquitination and ESCRT-0 stability during development, which is helpful to address the mechanisms of Hh signaling.
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Previous studies showed that Hrs is deubiquitinated by Ubpy.
26224310
Modified USP8 leads to the deubiquitination of SMO. 4 / 4
| 4
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Overexpression of Flag-USP8 in S2 cells reduced Smo ubiquitination (XREF_FIG, lane 3, top panel), whereas knockdown of USP8 by RNAi enhanced the levels of ubiquitinated Smo (XREF_FIG, lane 2, top panel), which was consistent with the data from the screen.
22253573
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Consistent with UBPY being able to counteract Smo ubiquitination independent of Hh signaling states, overexpression of UBPY reduced Smo ubiquitination in S2 cells both in the absence and presence of Hh (XREF_FIG).
22253574
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The overexpression of USP8 down-regulated Smo ubiquitination and increased Smo accumulation.
22253573
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Moreover, overexpression of USP8 prevents Smo ubiquitination and elevates Smo accumulation, leading to increased Hh signaling activity.
22253573
USP8 deubiquitinates STAM. 4 / 4
1 | 3
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USP8 modulates EGFR trafficking by regulating STAM de-ubiquitination on early endosomes 11.
26459808
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In addition, we identified STAM and NFX1, which are known to be deubiquitylated by USP8 and USP9 respectively.
33417828
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USP8 deubiquitinates STAM, preventing its degradation by the proteasome [XREF_BIBR], and Nrdp1, an E3 required for the lysosomal degradation of EGFR family members ErbB3 and ErbB4 [XREF_BIBR].
23845989
ubibrowser
UBPY function is essential for effective downregulation but is likely to be multifaceted, encompassing activity against both K63-linked and K48-linked polyubiquitin chains and including regulation of the stability of ESCRT-associated proteins such as STAM, by reversing their ubiquitination.
16996268
USP8 deubiquitinates KCNN4. 3 / 3
1 | 2
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Further, overexpression of wild-type USP8 accelerates channel deubiquitylation, while either a catalytically inactive mutant USP8 or siRNA mediated knockdown of USP8 enhanced accumulation of ubiquitylated KCa3.1, thereby inhibiting channel degradation.
21828287
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Further, we demonstrated that KCa3.1 is initially ubiquitylated following endocytosis and then deubiquitylated by USP8 prior to lysosomal degradation XREF_BIBR.
24632741
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27775833
USP8 deubiquitinates GJA1. 3 / 3
1 | 2
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USP8 reduces both multiple monoubiquitination and polyubiquitination of Cx43 to prevent autophagy mediated degradation.
29626091
ubibrowser
The ubiquitin-specific protease USP8 deubiquitinates and stabilizes Cx43
29626091
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USP8 interacts with and deubiquitinates Cx43, removing monoubiquitin moieties as well as K63- and K48 linked ubiquitin chains.
30126257
USP8 deubiquitinates EGFR phosphorylated on Y1172, Y1110, K867, K737, K754, K929, Y1092, Y1016, Y1197, K970, and Y1069 on K716. 3 / 3
3 |
biopax:pid
No evidence text available
17121848
biopax:pid
No evidence text available
17052190
biopax:pid
No evidence text available
16120644
USP8 deubiquitinates KDR. 3 / 3
| 3
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USP8 depleted endothelial cells displayed altered VEGFR2 ubiquitination and production of a unique VEGFR2 extracellular domain proteolytic fragment caused by VEGFR2 accumulation in the endosome-lysosome system.
26459808
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We now provide evidence that USP8 de-ubiquitinates VEGFR2.
26459808
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Conversely, the de-ubiquitinating enzyme, USP8, is shown to mediate de-ubiquitination of VEGFR2, regulating VEGFR2 trafficking, proteolysis, and signal transduction 39.
30120232
USP8 deubiquitinates EGFR phosphorylated on Y1172, Y1110, K737, K754, K929, Y1092, Y1016, K716, Y1197, K970, and Y1069 on K867. 3 / 3
3 |
biopax:pid
No evidence text available
17052190
biopax:pid
No evidence text available
17121848
biopax:pid
No evidence text available
16120644
USP8 deubiquitinates EGFR phosphorylated on Y1172, Y1110, K867, K737, K754, K929, Y1092, Y1016, K716, Y1197, and Y1069 on K970. 3 / 3
3 |
biopax:pid
No evidence text available
16120644
biopax:pid
No evidence text available
17121848
biopax:pid
No evidence text available
17052190
USP8 deubiquitinates ERBB2. 3 / 3
1 | 2
ubibrowser
ERBB2 is a target for USP8-mediated deubiquitination
21044682
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We recently showed that Usp8 also deubiquitinates ERBB2, albeit to a much lesser extent than EGFR [17].
23333852
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We recently showed that Usp8 also deubiquitinates ErbB2, albeit to a much lesser extent than EGFR [10].
22800866
USP8 deubiquitinates SEC31A. 3 / 3
1 | 2
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We concluded that USP8 deubiquitinates Sec31A and inhibits the formation of large COPII carriers, thereby suppressing collagen IV secretion.
29604273
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Ubiquitin-specific protease 8 deubiquitinates Sec31A and decreases large COPII carriers and collagen IV secretion
29604273
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Here, we show that the deubiquitinating enzyme USP8 interacts with and deubiquitinates Sec31A.
29604273
USP8 deubiquitinates EGFR phosphorylated on Y1172, Y1110, K867, K754, K929, Y1092, Y1016, K716, Y1197, K970, and Y1069 on K737. 3 / 3
3 |
biopax:pid
No evidence text available
16120644
biopax:pid
No evidence text available
17052190
biopax:pid
No evidence text available
17121848
USP8 deubiquitinates LRIG1. 3 / 3
1 | 2
ubibrowser
Review
28279784
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To determine whether endogenous USP8 deubiquitinates LRIG1, we used shUSP8 to decrease the level of endogenous USP8 in EBC1 cells.
24828152
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Also, when over-expressed, USP8 decreases LRIG1 ubiquitination by SAIT301 treatment (XREF_FIG).
24828152
USP8 deubiquitinates NTRK2. 3 / 3
| 1 2
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TrkB deubiquitination by USP8 regulates receptor levels and BDNF dependent neuronal differentiation.
33288548
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TrkB deubiquitination by USP8 regulates receptor levels and BDNF-dependent neuronal differentiation.
33288548
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TrkB deubiquitination by USP8 regulates receptor levels and BDNF dependent neuronal differentiation.
34005517
USP8 deubiquitinates EGFR phosphorylated on Y1172, Y1110, K867, K737, K929, Y1092, Y1016, K716, Y1197, K970, and Y1069 on K754. 3 / 3
3 |
biopax:pid
No evidence text available
17052190
biopax:pid
No evidence text available
17121848
biopax:pid
No evidence text available
16120644
USP8 deubiquitinates RNF41. 3 / 3
1 | 2
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We found that the carboxy terminal domain of Nrdp1 binds to the rhodanese domain of USP8, and that USP8 very efficiently deubiquitinates and stabilizes Nrdp1.
20868762
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USP8 deubiquitinates STAM, preventing its degradation by the proteasome [XREF_BIBR], and Nrdp1, an E3 required for the lysosomal degradation of EGFR family members ErbB3 and ErbB4 [XREF_BIBR].
23845989
ubibrowser
Review
27775833
USP8 deubiquitinates EGFR phosphorylated on Y1172, Y1110, K867, K737, K754, Y1092, Y1016, K716, Y1197, K970, and Y1069 on K929. 3 / 3
3 |
biopax:pid
No evidence text available
17052190
biopax:pid
No evidence text available
16120644
biopax:pid
No evidence text available
17121848
USP8 deubiquitinates SHANK3. 3 / 3
1 | 2
ubibrowser
USP8 Deubiquitinates SHANK3 to Control Synapse Density and SHANK3 Activity-Dependent Protein Levels
29735556
reach
USP8 acts to deubiquitinate SHANK3, which prevents its proteasomal mediated degradation and enhances overall dendritic spine stability.
29735556
reach
USP8 Deubiquitinates SHANK3 to Control Synapse Density and SHANK3 Activity Dependent Protein Levels.
29735556
USP8 deubiquitinates ITCH. 2 / 2
1 | 1
reach
USP8 and USP9X deubiquitinate ITCH to induce ubiquitination and degradation of the anti-apoptotic protein c-FLIP, leading to apoptosis in glioblastoma [XREF_BIBR], or to anoikis in pancreatic ductal adenocarcinoma [XREF_BIBR].
27203743
ubibrowser
Review
27775833
USP8 leads to the deubiquitination of F2RL1. 2 / 2
1 | 1
ubibrowser
Expression of the catalytically inactive mutants, AMSH(D348A) and UBPY(C786S), caused an increase in PAR(2) ubiquitination and trapped the receptor in early endosomes, thereby preventing lysosomal trafficking and degradation.
19684015
reach
USP8 and AMSH mediate deubiquitination of PAR2 and its sorting from endosomes to lysosomes [XREF_BIBR].
28448471
USP8 deubiquitinates GRIA. 2 / 2
| 2
reach
Furthermore, shRNA mediated knockdown of USP8 is sufficient to enhance the basal level of AMPAR ubiquitination in primary neurons.
29123470
reach
In addition to USP46, USP8 can also deubiquitinate mammalian AMPARs indicating that multiple regulatory mechanisms exist to control AMPAR ubiquitination levels (Scudder et al., 2014).
29302259
USP8 deubiquitinates HIF1A. 2 / 2
1 | 1
reach
HIF1alpha deubiquitination by USP8 is essential for ciliogenesis in normoxia.
24378640
ubibrowser
Review
28279784
USP8 deubiquitinates LEPR. 2 / 2
| 2
reach
Bland and colleagues suggested that leptin increases the expression of USP8, which in turn deubiquitylates the leptin receptor by cleaving Lys48-ubiquitin chains, among other (still unknown) chain types.
33483467
reach
USP8 deubiquitinates the leptin receptor and is necessary for leptin mediated synapse formation.
31199479
USP8 deubiquitinates EPG5. 2 / 2
1 | 1
reach
We propose that deubiquitination of EPG5 by USP8 guards the autophagic flux in ESCs to maintain their stemness.
30931944
ubibrowser
Mechanistically, USP8 directly removes non-classical K63-linked ubiquitin chains from EPG5 at Lysine 252, leading to enhanced interaction between EPG5 and LC3.
30931944
USP8 deubiquitinates SNCA. 2 / 2
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ubibrowser
In addition, this study identifies USP8 as one of the best markers of Lewy bodies in human pigmented neurons in sporadic cases of Parkinson’s disease and demonstrates the ability of USP8 to hydrolyze K63-linked ubiquitin chains from α-synuclein in vitro
30126257
ubibrowser
Another deubiquitinase, USP8, removes K63-linked ubiquitin chains of α-synuclein and prevents its lysosomal degradation.
27444016
Mutated USP8 leads to the deubiquitination of EGFR. 2 / 2
| 2
reach
The identified USP8 mutants increase EGFR deubiquitination to inhibit EGF induced EGFR downregulation, leading to augmented and more sustained EGFR signaling.
26285834
reach
USP8 mutants diminished epidermal growth factor receptor ubiquitination and induced Pomc promoter activity in immortalized AtT-20 corticotropinoma cells.
25942478
USP8 leads to the deubiquitination of ARL6IP4. 2 / 2
| 2
reach
Consistent with this idea, overexpression of wild-type USP8 decreased the ubiquitination of the FLIP (S) E3 ubiquitin ligase AIP4, an event previously shown to increase AIP4-FLIP (S) interaction, whereas siRNA mediated suppression of USP8 increased AIP4 ubiquitination.
20484045
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Consistent with this idea, over-expression of WT USP8 decreased ubiquitination of the FLIP S E3 ubiquitin ligase AIP4, an event previously shown to increase AIP4-FLIP S interaction, while siRNA mediated suppression of USP8 increased AIP4 ubiquitination.
20484045
USP8 deubiquitinates CYT1. 2 / 2
| 2
reach
Finally, even though CYT-1 shows ligand induced K63 polyubiquitination, it is not subjected to deubiquitination by the K63 polyubiquitin specific AMSH deubiquitinating enzyme, while CYT-1 is slightly deubiquitinated by USP8.
23153581
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Finally, CYT-1 is not subjected to deubiquitination by the K63 polyubiquitin specific AMSH DUB enzyme, while CYT-1 is slightly deubiquitinated by USP8.
23153581
USP8 deubiquitinates RNF128. 2 / 2
| 2
reach
These data further demonstrate that the two isoforms of Otubain 1 have opposing effects on GRAIL and that Otubain 1 ARF-1 recruits the ubiquitin specific protease 8 (USP-8) to promote GRAIL deubiquitination and stabilization.
24917867
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This unexpected function of otubain-1 might be mediated through the inhibition of USP8, a DUB that binds to and deubiquitylates GRAIL; however, it is not known how otubain-1 might inhibit USP8.
18535581
USP8 leads to the deubiquitination of CFLAR. 2 / 2
1 | 1
ubibrowser
USP8 directly deubiquitylates and stabilizes FLIPL
27321185
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USP8 and USP9X deubiquitinate ITCH to induce ubiquitination and degradation of the anti-apoptotic protein c-FLIP, leading to apoptosis in glioblastoma [XREF_BIBR], or to anoikis in pancreatic ductal adenocarcinoma [XREF_BIBR].
27203743
USP8 deubiquitinates EPS15. 2 / 2
1 | 1
reach
UBPY also deubiquitinated Eps15 in vitro, suggesting that Eps15 is a cellular substrate for UBPY.
16771824
ubibrowser
No evidence text available
USP8 deubiquitinates LDLR. 2 / 2
1 | 1
reach
We further show that USP8 acts downstream of IDOL to deubiquitinate LDLR and that USP8 is required for LDLR entry into the MVB pathway.
23382078
ubibrowser
We further show that USP8 acts downstream of IDOL to deubiquitinate LDLR and that USP8 is required for LDLR entry into the MVB pathway.
23382078
USP8 deubiquitinates FZD5 on lysine. 1 / 1
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biopax:reactome
No evidence text available
USP8 deubiquitinates LRIG1 on lysine. 1 / 1
1 |
biopax:reactome
No evidence text available
USP8 deubiquitinates GRIA1. 1 / 1
1 |
ubibrowser
Synaptic Strength Is Bidirectionally Controlled by Opposing Activity-Dependent Regulation of Nedd4-1 and USP8
25505317
USP8 deubiquitinates SFRP4. 1 / 1
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ubibrowser
Review
27775833
USP8 deubiquitinates CBL-Y1045F. 1 / 1
| 1
reach
Indeed, the Y1045F and Y1091F Cbl binding site mutants are deubiquitinated by Usp8, suggesting that this ubiquitination signal may represent mono- or oligo-ubiquitin (Figs. 7 and 8, upper panel, arrow[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
21044682
USP8 deubiquitinates KIF23. 1 / 1
1 |
ubibrowser
No evidence text available
USP8 deubiquitinates CBL. 1 / 1
| 1
reach
The Cbl binding site mutants of EGFR (Y1045F) and EGFR-ErbB2 (Y1091F) are also deubiquitinated by Usp8 both with and without EGF stimulation (Figs. 7 and 8).
21044682
USP8 deubiquitinates Smoothened. 1 / 1
| 1
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Smoothened, a key component of Hedgehog pathway, is deubiquitinated by USP8 34 and activation of Hedgehog pathway induces ACTH secretion 35.
25675982
USP8 leads to the deubiquitination of TRAF6. 1 / 1
| 1
reach
USP8 induces the deubiquitination of TRAF6, TAB2, TAK1, p62, and BECN1, which are pivotal roles for NF-κB activation and autophagy induction.
34688043
USP8 deubiquitinates EGFR-Y1045F. 1 / 1
| 1
reach
The Cbl binding site mutants of EGFR (Y1045F) and EGFR-ErbB2 (Y1091F) are also deubiquitinated by Usp8 both with and without EGF stimulation (Figs. 7 and 8).
21044682
USP8 deubiquitinates ERVK-18. 1 / 1
| 1
reach
Furthermore we demonstrated that both EGFR and EGFR-ErbB2 TM are deubiquitinated by the deubiquitination enzyme Usp8, although deubiquitination of ErbB2 was less efficient than that of EGFR [10].
22800866
USP8 deubiquitinates EGF. 1 / 1
| 1
reach
However, we can not fully exclude the other possibility that the UBPY S680A expression resulted in a reduction in the cellular Ub conjugating activity toward activated EGFR in some way.The fact that U[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
17720156
USP8 deubiquitinates FZD. 1 / 1
| 1
reach
In contrast, Fzd receptors are deubiquitinated by UBPY and ubiquitin specific protease 6 and 8 (USP6 and USP8).
| PMC
USP8 deubiquitinates ERBB3. 1 / 1
1 |
ubibrowser
USP8 regulates another EGFR family member, ErbB3 by modulating Nrdp1 (neuregulin-receptor-degradation protein-1)
25121098
USP8 deubiquitinates BIRC6. 1 / 1
1 |
ubibrowser
No evidence text available
USP8 deubiquitinates NTRK1. 1 / 1
1 |
ubibrowser
Recent studies have attempted to identify the specific DUBs associated with TrkA, where Ceriani and collaborators described an interaction between TrkA and USP8 (USP-family) in PC12 cells
28335430
USP8 deubiquitinates CASP8. 1 / 1
| 1
reach
Our data are consistent with the recent findings that USP8 directly deubiquitylates and stabilizes the long isoform of FLICE like inhibitory protein (FLIP L) in cervical cancer cell line ME-180, which was derived from the metastatic site of epidermoid carcinoma.
30010158
USP8 deubiquitinates CFTR. 1 / 1
| 1
reach
For example, in this and a previous study we observed that neither USP34, nor USP8 deubiquitinate CFTR, and only USP10 activity was inhibited by Cif XREF_BIBR, XREF_BIBR.
21455491
USP8 deubiquitinates MET. 1 / 1
1 |
ubibrowser
Review
27919796
USP8 deubiquitinates NFX1. 1 / 1
| 1
reach
In addition, we identified STAM and NFX1, which are known to be deubiquitylated by USP8 and USP9 respectively.
33417828
USP8 deubiquitinates MCPH1. 1 / 1
1 |
ubibrowser
BRUCE regulates DNA double-strand break response by promoting USP8 deubiquitination of BRIT1
25733871
USP8 deubiquitinates FZD4 on lysine. 1 / 1
1 |
biopax:reactome
No evidence text available
USP8 leads to the deubiquitination of BECN1. 1 / 1
| 1
reach
USP8 induces the deubiquitination of TRAF6, TAB2, TAK1, p62, and BECN1, which are pivotal roles for NF-κB activation and autophagy induction.
34688043
USP8 deubiquitinates SCNN1A. 1 / 1
1 |
ubibrowser
USP8 interacted with ENaC, as detected by co-immunoprecipitation, and it deubiquitinated ENaC.
23297398
USP8 in the endosome deubiquitinates EGFR in the endosome. 1 / 1
| 1
trips
We conclude that UBPY negatively regulates the rate of EGFR down-regulation by deubiquitinating EGFR on endosomes.
16120644
USP8 leads to the deubiquitination of TCHP. 1 / 1
| 1
reach
Conversely, deubiquitination of TCHP is mediated by ubiquitin-specific peptidase 8 (USP8) [50].
| PMC
USP8 deubiquitinates BACE1. 1 / 1
1 |
ubibrowser
The Endosome-associated Deubiquitinating Enzyme USP8 Regulates BACE1 Enzyme Ubiquitination and Degradation
27302062
Modified USP8 leads to the deubiquitination of LRIG1. 1 / 1
| 1
reach
SAIT301 treatment significantly enhanced the ubiquitination of LRIG1, whereas over-expression of USP8 markedly diminished the ubiquitination of LRIG1 (XREF_FIG).
24828152
Threonine-phosphorylated USP8 deubiquitinates RNF41. 1 / 1
1 |
biopax:pid
No evidence text available
17210635
USP8 deubiquitinates USP46. 1 / 1
| 1
reach
In addition to USP46, USP8 can also deubiquitinate mammalian AMPARs indicating that multiple regulatory mechanisms exist to control AMPAR ubiquitination levels (Scudder et al., 2014).
29302259
USP8 deubiquitinates FZD8 on lysine. 1 / 1
1 |
biopax:reactome
No evidence text available
USP8 deubiquitinates CBL-Y1091F. 1 / 1
| 1
reach
Indeed, the Y1045F and Y1091F Cbl binding site mutants are deubiquitinated by Usp8, suggesting that this ubiquitination signal may represent mono- or oligo-ubiquitin (Figs. 7 and 8, upper panel, arrow[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
21044682
USP8 deubiquitinates FLIP. 1 / 1
| 1
reach
USP8 directly deubiquitylates and stabilizes FLIP L, but not the short isoform.
27321185
Mutated USP8 leads to the deubiquitination of TARDBP. 1 / 1
| 1
reach
Moreover, wild-type but not active site mutant UBPY reduced ubiquitination of TDP-43 C-terminal fragments and of a nuclear import impaired mutant.
24825905
Ubiquitinated USP8 deubiquitinates RNF128. 1 / 1
| 1
reach
These data suggest a reciprocal E3-DUB relationship in which GRAIL can ubiquitinate USP8, and ubiquitinated USP8 can de-ubiquitinate GRAIL.
21078124
USP8 deubiquitinates FZD6 on lysine. 1 / 1
1 |
biopax:reactome
No evidence text available
USP8 leads to the deubiquitination of TARDBP. 1 / 1
| 1
reach
In D. melanogaster models, the ubiquitin conjugating enzyme UBE2E3 promotes ubiquitination of TDP-43; in contrast, ubiquitin isopeptidase Y (UBPY) decreased TDP-43 ubiquitination.
27693252

Other Statements

psp cbn pc bel_lc signor biogrid tas hprd trrust ctd vhn pe drugbank omnipath conib crog dgi minerva creeds ubibrowser acsn | geneways tees gnbr semrep isi trips rlimsp medscan eidos sparser reach
USP8 affects EGFR
| 37
USP8 activates EGFR.
| 22
USP8 activates EGFR. 10 / 19
| 17
reach
USP8 depletion accelerates receptor turnover, whereas loss of hepatocyte growth factor regulated substrate (Hrs) rescues this phenotype, indicating that USP8 protects EGFR from degradation via an Hrs dependent pathway.
20736164
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Previous work reported that USP8 depletion severely inhibits EGFR degradation 11.
26459808
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Other studies have suggested that mutations in USP8 reduce the degradation of EGFR, such as HER-2 and HER-3, thereby promoting tumor progression.
32848421
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Finally, depletion of endogenous UBPY by RNA interference resulted in elevated ubiquitination and accelerated degradation of EGF activated EGFR.
16120644
reach
Nevertheless, both AMSH [31, 34, 35] and UBPY [32, 33, 36-38] have been reported to increase EGFR down-regulation.
29981430
reach
We propose a model in which the coordinated action of UBE4B, ESCRT-0, and the deubiquitinating enzyme USP8 enable the endosomal sorting and lysosomal degradation of the EGFR.
24344129
reach
In other studies, both AMSH XREF_BIBR, XREF_BIBR and UBPY XREF_BIBR, XREF_BIBR, XREF_BIBR have been reported to increase EGFR down-regulation.
22710717
reach
USP8 knockdown leads to reduce EGFR protein and inhibits ACTH secretion.
29765354
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Whereas USP8 variants increase EGFR signaling in cultured cells, such an effect has not been consistently shown in vivo, suggesting that the effect is small or temporary or that other factors [XREF_BIBR] are involved in increased ACTH production and/or proliferation of USP8 mutation positive tumors.
29600293
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Depletion of UBPY, another DUB that associates with ESCRT components, has been shown to both accelerate and slow the rate of EGFR degradation.
24456136
Mutated USP8 activates EGFR. 5 / 5
| 5
reach
We found that USP8 mutated PAs have a higher incidence of EGFR expression, increased EGFR protein abundance and activation of downstream Erk1/2, indicating that USP8 mutations enhance EGFR signaling in tumors.
25675982
reach
In human corticotroph primary cultures, treatment with the pan-ErbB TKI canertinib as well as the EGFR TKI gefitinib suppresses POMC mRNA, and USP8 mutations, detected in up to two-thirds of CD, may underlie the increase in EGFR signaling in these tumors.
28520590
reach
USP8 mutations, detected in up to two-thirds of Cushing disease, may underlie the increase in EGFR signalling in these tumours.
28520590
reach
The USP8 mutation (14-3-3 somatic mutations) inhibits EGFR degradation, enhances EGFR accumulation, and consequently, likely induces corticotroph EGFR tumor signaling.
29264472
reach
Considering that activation of EGFR-MAPK signaling induces p27 (Kip1) degradation, and p27 (Kip1)-deficient mice develop corticotropinoma XREF_BIBR, XREF_BIBR, we speculate that through activating EGFR signaling USP8 mutation accelerates p27 (Kip1) degradation, representing an important molecular mechanism underlying ACTH hyperproduction (XREF_FIG).
25675982
USP8 inhibits EGFR.
| 7
USP8 inhibits EGFR. 7 / 9
| 7
reach
In keeping with this intermediate phenotype, UBPY depletion partially reduced the interaction of EGFR with ESCRT-III.
23477725
reach
While one report suggests that Usp8 inhibits EGFR degradation [25], we and others have demonstrated that Usp8 promotes EGFR degradation [21,26].
23333852
reach
By the same mechanism, USP8 also directs the trafficking and lysosomal degradation of CXCR4 [XREF_BIBR], MET and epidermal growth factor receptor [XREF_BIBR, XREF_BIBR], implying that its loss consequent to increased RNF41 abundance would prolong and potentially amplify invasion signaling by these receptors.
26231668
reach
By removing the lysosomal sorting signal, UBPY negatively regulates the downregulation of EGFR [10].
17720156
reach
While some reports suggest that Usp8 inhibits EGFR degradation [40], we and others demonstrated that Usp8 stimulates EGFR degradation [41,42].
21044682
reach
USP8 has been shown to have opposing effects on EGF receptor degradation by either directly deubiquitinating receptors to prevent their degradation, or by deubiquitinating ESCRT complex proteins to stabilize them and thus promote EGF receptor degradation [XREF_BIBR, XREF_BIBR, XREF_BIBR - XREF_BIBR].
23316392
reach
Depletion of USP8 with siRNA inhibits EGFR activation and increases EGFR degradation [32], similar to the effect of depleting SEPW1, and suggests the possibility SEPW1 might regulate USP8.
25721765
USP8 increases the amount of EGFR.
| 6
USP8 increases the amount of EGFR. 5 / 5
| 5
reach
Consistently, the expression of EGFR was decreased by genetic silencing of USP8.
30010158
reach
Western blotting confirmed that knockdown of USP8 not only reduced RTK phosphorylation, but also the total levels of EGFR, ERBB2, ERBB3, and MET in H1975 and H1650 cells (XREF_FIG).
23748694
reach
Taken together, our findings demonstrate for the first time that inhibition of USP8 down-regulates the total protein levels of EGFR, ERBB2, ERBB3, and MET, and effectively attenuates related RTK signaling pathways.
23748694
reach
USP8 knockdown in primary ACTH secreting tumor cells, however, reduced ACTH secretion and EGFR levels, suggesting that inhibition of USP8 activity may be an effective treatment strategy for CD.
27569239
reach
Moreover, USP8 knockdown reduced EGFR protein level in USP8 mutated tumor cells (XREF_SUPPLEMENTARY).
25675982
Modified USP8-C748A increases the amount of ubiquitinated EGFR. 1 / 1
| 1
reach
We previously showed that overexpression of the Usp8 C748A mutant strongly enhances accumulation of the steady state level of ubiquitinated EGFR in the absence of EGF [41].
21044682
USP8 decreases the amount of EGFR.
| 2
USP8 decreases the amount of EGFR. 1 / 3
| 1
reach
Importantly, USP8 inactivation attenuated ACTH secretion and EGFR expression in primary tumor cells.
25675982
Modified USP8 decreases the amount of EGFR. 1 / 1
| 1
reach
Overexpression of UBPY reduced the ubiquitination level of EGFR and delayed its degradation in EGF stimulated cells.
16120644
USP8 affects SMO
| 22
USP8 activates SMO.
| 11
USP8 activates SMO. 9 / 18
| 9
reach
The stimulation of Hh promotes Smo deubiquitination by ubiquitin specific protease 8 (USP8), which blocks Smo endocytosis and enhances Smo cell surface accumulation XREF_BIBR XREF_BIBR.
28195188
reach
Overexpression of USP8 caused an elevation of Smo in both A- and P-compartment cells but did not ectopically activate Hh target genes, such as ptc, in A-compartment cells located away from the A/P boundary (XREF_FIG).
22253573
reach
In addition, a gain-of-function experiment showed that the overexpression of USP8 caused an accumulation of Smo in both A- and P-compartment cells (XREF_FIG) and caused anterior expansion of ptc-lacZ in cells that received Hh (XREF_FIG).
22253573
reach
We next wished to assess whether the accumulation of Smo induced by the overexpression of USP8 or the inactivation of Shi was due to changes in the cell surface accumulation of Smo.
22253573
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We revealed that overexpression of usp8 blocked rack1 RNAi induced Smo degradation, suggesting that Rack1 positively regulates Smo possibly through Usp8.
32467643
reach
These data suggest that USP8 promotes the cell surface accumulation of Smo, and that Shi mediates Smo endocytosis.
22253573
reach
USP8 Promotes Smo Signaling Activity.
22253573
reach
USP8 Promotes Smo Accumulation in Wing Imaginal Discs.
22253573
reach
It is also possible that USP8 promotes Smo recycling to the cell surface.
22253573
Modified USP8 activates SMO. 2 / 2
| 2
reach
The overexpression of USP8 down-regulated Smo ubiquitination and increased Smo accumulation.
22253573
reach
Moreover, overexpression of USP8 prevents Smo ubiquitination and elevates Smo accumulation, leading to increased Hh signaling activity.
22253573
USP8 inhibits SMO.
| 3
USP8 inhibits SMO. 3 / 10
| 3
reach
USP8 Prevents the Localization of Smo to the Early Endosome.
22253573
reach
The stimulation of Hh promotes Smo deubiquitination by ubiquitin specific protease 8 (USP8), which blocks Smo endocytosis and enhances Smo cell surface accumulation XREF_BIBR XREF_BIBR.
28195188
reach
Moreover, we found that USP8 prevents Smo localization to early endosomes that are labeled with Rab5.
22253573
USP8 increases the amount of SMO.
| 5
USP8 increases the amount of SMO. 3 / 3
| 3
reach
We also provide evidence that the non visual beta-arrestin Kurtz (Krz) acts in parallel with Smo ubiquitination to control Smo cell surface expression, and that the deubiquitinating enzyme UBPY promotes Smo cell surface expression by counteracting Smo ubiquitination.
22253574
reach
Our explanation is that the increase in Smo levels that was induced by USP8 was still inhibited by Ptc, since we found that USP8 induced more severe overgrowth phenotypes in the ptc mutant background (XREF_FIG).
22253573
reach
UBPY may modulate Smo cell surface expression by attenuating Smo endocytosis and/or promoting Smo recycling (XREF_FIG).
22253574
Modified USP8 increases the amount of SMO. 2 / 2
| 2
reach
However, although the overexpression of USP8 increased the levels of Smo in vivo, it failed to induce Hh target gene expression in A-compartment cells located away from the A/P boundary.
22253573
reach
Overexpression of USP8 elevated the level of Smo but did not induce ectopic Hh signaling activity in A compartment cells located away from the A/P boundary.
22253573
USP8 decreases the amount of SMO.
| 3
USP8 decreases the amount of ubiquitinated SMO. 1 / 1
| 1
reach
Overexpression of Flag-USP8 in S2 cells reduced Smo ubiquitination (XREF_FIG, lane 3, top panel), whereas knockdown of USP8 by RNAi enhanced the levels of ubiquitinated Smo (XREF_FIG, lane 2, top panel), which was consistent with the data from the screen.
22253573
Modified USP8 decreases the amount of ubiquitinated SMO. 1 / 1
| 1
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In agreement with this hypothesis, the overexpression of HA-USP8 reversed the effects of Flag-USP8C> S and again reduced the levels of ubiquitinated Smo (XREF_FIG, lane 4, top panel).
22253573
Modified USP8 decreases the amount of SMO. 1 / 1
| 1
reach
The overexpression of USP8 decreased the amount of Smo that co-localized with Rab5 (XREF_FIG), which suggested that USP8 may prevent the accumulation of Smo in early endosomes and therefore promote the cell surface accumulation of the protein (XREF_FIG) as well as increase the signaling activity (XREF_FIG).
22253573
USP8 inhibits cell population proliferation. 10 / 18
| 1 17
reach
We also observed that down-regulation of USP8 inhibited the proliferation of GC cells which highly expressed HER-3.
32848421
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Indeed, inhibition of USP8 either by its knockdown or synthetic small molecule led to attenuation of variety of receptor tyrosine kinase (RTK) activities, resulting in the inhibition of cell proliferation in gefitinib-resistant and -sensitive non-small cell lung cancer (NSCLC) cells [47] .
26077642
reach
USP8 Inhibitor Suppresses HER-2 Positive Gastric Cancer Cell Proliferation and Metastasis via the PI3K and AKT Signaling Pathway.
33116578
sparser
In conclusion, USP8 inhibitor could inhibit proliferation, abolishes clonogenic ability, and induces apoptosis in pituitary corticotroph tumor cell-AtT20 cells.
27569239
reach
Down-regulation of USP8 Inhibits Cholangiocarcinoma Cell Proliferation and Invasion.
32273758
reach
Erratum: Down-Regulation of USP8 Suppresses HER-3 Positive Gastric Cancer Cells Proliferation [Corrigendum].
34848972
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Both GADD45beta and CABLES1 may be responsible, at least in part, for the USP8 induced suppression of corticotroph tumor cell proliferation.
31666445
reach
Therefore, it was confirmed that down-regulation of USP8 could inhibit the proliferation of NCI-N87, MKN-45 and AGS cell lines, which is HER-3 positive GC cells.
32848421
reach
All in vitro results demonstrated that down-regulation of USP8 inhibited the proliferation and viability of GC cells with high expression of HER3 (NCI-N87, MKN-45 and AGS), but did not affect HER3 negative cells (MGC-803).
32848421
reach
Down-Regulation of USP8 Suppresses HER-3 Positive Gastric Cancer Cells Proliferation.
32848421
USP8 activates cell population proliferation. 8 / 8
| 8
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We demonstrated that knockdown of USP8 significantly inhibited the proliferation, migration and invasion of QBC939 and RBE cells in vitro, while USP8 overexpression showed significant promoting effects on Hucct-1 cells.
32273758
reach
Indeed, inhibition of USP8 either by its knockdown or synthetic small molecule led to attenuation of variety of receptor tyrosine kinase (RTK) activities, resulting in the inhibition of cell proliferation in gefitinib resistant and -sensitive non small cell lung cancer (NSCLC) cells [XREF_BIBR].
26077642
reach
However, although overexpressing USP8 in SiHa and SW756 cells enhanced cell proliferation, it did not reach statistical significance according to our data.
30010158
reach
KD of the EGF receptor (EGFR) in human RPE cells inhibits USP8 Tyr717 and Tyr810 phosphorylation, which enables TCHP and AURKA degradation and reverses the serum-induced effects on ciliogenesis and cell proliferation [50].
| PMC
reach
We will provide an overview of corticotroph tumorigenesis in the context of hypothalamic-pituitary-adrenal (HPA) axis regulation with an emphasis on the role of the glucocorticoid receptor in the resistance to the negative feedback of cortisol that occurs in CD, and we will explore the role of epidermal growth factor receptor (EGFR) signaling in ACTH hyper-secretion and corticotroph cell proliferation and the recent discovery of somatic ubiquitin specific peptidase 8 (USP8) mutations in a significant number of patients with sporadic CD with an emphasis on therapeutic implications.
28529722
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CCK-8 cell viability tests showed that USP8 can promote tumor cell proliferation, although statistical significance was not achieved (XREF_FIG).
30010158
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Cellular studies showed that USP8 can enhance the proliferation, migration, and invasion abilities of CSCC cells, thereby promoting tumor progression.
30010158
reach
Furthermore, by overexpressing or silencing USP8, cellular studies indicated that USP8 can directly upregulate the proliferation and metastatic abilities of CSCC cells.
30010158
USP8 affects apoptotic process
| 2 1 12
USP8 inhibits apoptotic process.
| 2 1 7
USP8 inhibits apoptotic process. 10 / 11
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Moreover, silencing of USP8 also promoted apoptosis in cholangiocarcinoma cells by regulating the Bcl-2 and Bax axis and Caspase cascade; up-regulation of USP8 decreased apoptosis in Hucct-1 cells.
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High expression of USP8 can therefore inhibit extrinsic apoptosis by stabilizing FLIP L [ xref ] .
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Consistently, knockdown of USP8 significantly increased apoptosis of PIK3CA mutant cells even in the presence of glutamine (XREF_SUPPLEMENTARY).
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In the present study , our objective is to study in broad the secondary down-stream effect after depleting USP5 or USP8 , which were initially showed to induce apoptosis in various cancers .
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Taken together, our data indicate that USP8 functions as a novel deubiquitylase of FLIP L and inhibits extrinsic apoptosis by stabilizing FLIP L.
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USP8 DUB prevents c-FLIP L, degradation and further halts the apoptosis in cancer cells suggesting it to be a potential drug target.
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High expression of USP8 can therefore inhibit extrinsic apoptosis by stabilizing FLIP L [XREF_BIBR].
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USP8 inhibition via genetic and pharmacological approaches resulted in growth inhibition and apoptosis induction in both sensitive and doxorubicin resistant HCC cells.
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Knockdown of USP8 inhibited the proliferation , migration , invasion , and cell cycle progression of A549 and H1299 cells , and promoted the apoptosis .
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Knockdown of USP8 inhibited the proliferation of human lung cancer cells by regulating cell cycle- and apoptosis related proteins.
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USP8 activates apoptotic process.
| 5
USP8 activates apoptotic process. 5 / 5
| 5
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The results indicated that the down-regulation of USP8 could significantly promote the apoptosis of NCI-N87 and MKN-45 cells, but it did not work on MGC-803 cells (XREF_FIG).
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These results indicated that down-regulation of USP8 could promote the apoptosis of HER3 positive GC cells and inhibit the proliferation of them by affecting the cell-cycle.
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Knockdown of USP8 inhibited the proliferation, migration, invasion, and cell cycle progression of A549 and H1299 cells, and promoted the apoptosis.
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In the present study, our objective is to study in broad the secondary down-stream effect after depleting USP5 or USP8, which were initially showed to induce apoptosis in various cancers.
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Moreover, down-regulation of USP8 could promote the apoptosis of HER3 positive GC cells and inhibit the proliferation of them by affecting the cell-cycle.
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USP8 affects POMC
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USP8 activates POMC.
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USP8 activates POMC. 8 / 8
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USP8 knockdown leads to reduce EGFR protein and inhibits ACTH secretion.
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USP8 mutated tumors are more common in females, and are associated with earlier onset, a smaller size, and increased ACTH production.
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For the first time, we showed that USP8 knockdown or gefitinib treatment significantly reduced ACTH secretion in primary USP8 mutated corticotrophin adenoma cells, but not in wild-type cells.
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We further showed that USP8 knockdown or gefitinib (a clinically available EGFR inhibitor) treatment significantly reduced ACTH secretion in primary USP8 mutated corticotrophin adenoma cells, but not in wild-type cells.
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Because EGFR signaling increases POMC transcription and secretion of ACTH [XREF_BIBR], increased USP8 activity causes elevated ACTH production.
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The presence of such associations is supported by the finding that USP8 knockdown or EGFR inhibition attenuates ACTH secretion in primary USP8 mutated tumor cells [XREF_BIBR].
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We will provide an overview of corticotroph tumorigenesis in the context of hypothalamic-pituitary-adrenal (HPA) axis regulation with an emphasis on the role of the glucocorticoid receptor in the resistance to the negative feedback of cortisol that occurs in CD, and we will explore the role of epidermal growth factor receptor (EGFR) signaling in ACTH hyper-secretion and corticotroph cell proliferation and the recent discovery of somatic ubiquitin specific peptidase 8 (USP8) mutations in a significant number of patients with sporadic CD with an emphasis on therapeutic implications.
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USP8 knockdown using shRNA in primary corticotroph adenoma cells effectively reduced ACTH production.
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Mutated USP8 activates POMC. 2 / 2
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It is expected that USP8 mutations deregulate these molecules to drive ACTH production and secretion.
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While USP8 mutations were less likely to enhance tumorous ACTH hypersecretion via EGFR mediated activation, the presence of USP8 mutations may predict favorable responses to the somatostatin analog pasireotide, which exhibits high affinity for SSTR5.
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USP8 inhibits POMC.
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Mutated USP8 inhibits POMC. 1 / 1
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It is expected that USP8 mutations deregulate these molecules to drive ACTH production and secretion.
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USP8 increases the amount of POMC.
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Mutated USP8 increases the amount of POMC. 1 / 1
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Ultimately, USP8 mutants lead to inhibition of EGF signaling downregulation and increased Pomc expression and ACTH secretion [XREF_BIBR, XREF_BIBR].
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USP8 affects ERBB3
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USP8 inhibits ERBB3.
| 3
USP8 inhibits ERBB3. 3 / 3
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Down-Regulation of USP8 Promotes the Degradation of HER-3.
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Erratum: Down-Regulation of USP8 Suppresses HER-3 Positive Gastric Cancer Cells Proliferation [Corrigendum].
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All these results indicated that down-regulation of USP8 could inhibit the proliferation of HER-3 positive cells, NCI-N87 and MKN-45, in vivo.
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USP8 increases the amount of ERBB3.
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USP8 increases the amount of ERBB3. 2 / 2
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These results are opposite of the results seen by Niendorf et al. [130] showing that deletion of USP8 leads to lower level of ERBB3.
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Western blotting confirmed that knockdown of USP8 not only reduced RTK phosphorylation, but also the total levels of EGFR, ERBB2, ERBB3, and MET in H1975 and H1650 cells (XREF_FIG).
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USP8 decreases the amount of ERBB3.
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USP8 decreases the amount of ERBB3. 2 / 2
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Down-regulation of USP8 inhibited cell proliferation and cell metastasis and also reduced the HER-3 expression.
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USP8 or USP9X silencing increased HER3 protein level in basal conditions (medium alone) in BxPC3 cells, suggesting that each deubiquitinase promotes basal HER3 degradation by stabilizing ITCH, as proposed for USP8 [XREF_BIBR].
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USP8 activates ERBB3.
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USP8 activates ERBB3. 2 / 2
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These results indicated that down-regulation of USP8 could promote the apoptosis of HER3 positive GC cells and inhibit the proliferation of them by affecting the cell-cycle.
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Moreover, down-regulation of USP8 could promote the apoptosis of HER3 positive GC cells and inhibit the proliferation of them by affecting the cell-cycle.
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USP8 affects cell growth
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USP8 activates cell growth. 5 / 8
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In contrast, USP8 knockdown suppressed melanoma cell growth, survival and migration, and augmented the inhibitory effects of therapeutic drugs.
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USP8 was originally identified to enhance cell growth as its expression increases upon serum stimulation in cancer cells.
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USP8 is known to enhance cell growth as its expression increases in cancer cell XREF_BIBR.
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Small molecule inhibitors of USP8 (HBX90,397 and HBX 90,659) have been shown to inhibit HCT116 and PC3 cell growth, and to display specificity for USP8 among a panel of cysteine proteases [XREF_BIBR].
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XREF_BIBR Ubiquitin specific peptidases (USP8) was originally identified to enhance cell growth as its expression increases upon serum stimulation in cancer cells.
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USP8 affects RNF41
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USP8 activates RNF41. 3 / 8
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Since Nrdp1 targets USP8 for ubiquitylation, we speculated that overexpression of Nrdp1 could enhance protein ubiquitylation and USP8 degradation in PC12 cells.
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USP8 markedly enhanced the stability of Nrdp1, and a point mutant that disrupts USP8 catalytic activity destabilized endogenous Nrdp1.
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Our results indicate that Nrdp1 is a specific target for the USP8 deubiquitinating enzyme and are consistent with a model where USP8 augments Nrdp1 activity by mediating its stabilization.
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USP8 activates Neoplasm Invasiveness.
| 6
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Moreover, we conducted cellular studies and found that USP8 can significantly upregulate the migration and invasion processes of CSCC cell lines.
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USP8 promotes CSCC progression by enhancing tumor invasion capacity.
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However, both the migration and invasion capacities of CSCC cells were upregulated by USP8 overexpression (XREF_FIG).
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In conclusion, we demonstrated that USP8 in cancer tissue is an independent prognostic biomarker of CSCC, and high USP8 in CSCC can enhance cell invasion.
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We demonstrated that knockdown of USP8 significantly inhibited the proliferation, migration and invasion of QBC939 and RBE cells in vitro, while USP8 overexpression showed significant promoting effects on Hucct-1 cells.
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Cellular studies showed that USP8 can enhance the proliferation, migration, and invasion abilities of CSCC cells, thereby promoting tumor progression.
30010158
USP8 inhibits Neoplasm Invasiveness.
| 2
USP8 inhibits Neoplasm Invasiveness. 2 / 2
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Down-regulation of USP8 Inhibits Cholangiocarcinoma Cell Proliferation and Invasion.
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Knockdown of USP8 inhibited the proliferation, migration, invasion, and cell cycle progression of A549 and H1299 cells, and promoted the apoptosis.
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EGFR affects USP8
| 3 5
EGFR activates USP8. 7 / 7
| 3 4
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EGFR activates USP8 by phosphorylating Tyr 717 and Tyr 810.
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EGFR activation causes USP8 to become phosphorylated and to associate with EGFR on endosomes where it dynamically regulates EGFR ubiquitination state during trafficking.
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Most importantly, epidermal growth factor receptor (EGFR) kinase activated USP8 by phosphorylating Tyr 717 and Tyr 810.
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Importantly, GST-EGFR phosphorylated non-tagged USP8 and elevated its DUB activity toward ubiquitin oligomers (Fig.  xref ; lanes 1–3), but GST-EGFR did not activate GST-USP8 (Supplementary Fig.  xref ).
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Taken together, EGFR activates USP8 by directly phosphorylating Tyr 717 and -810 in vitro.
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EGFR activates USP8 by phosphorylating Tyr-717 and Tyr-810.
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Taken together, EGFR activates USP8 by directly phosphorylating Tyr-717 and −810 in vitro.
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EGFR activates mutated USP8. 1 / 1
| 1
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Considering that activation of EGFR-MAPK signaling induces p27 (Kip1) degradation, and p27 (Kip1)-deficient mice develop corticotropinoma XREF_BIBR, XREF_BIBR, we speculate that through activating EGFR signaling USP8 mutation accelerates p27 (Kip1) degradation, representing an important molecular mechanism underlying ACTH hyperproduction (XREF_FIG).
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USP8 affects Ubiquitin
| 7
USP8 activates Ubiquitin.
| 4
USP8 activates Ubiquitin. 4 / 4
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USP8 enhances mitophagy by removing lysine-6-linked ubiquitin from parkin, promoting its turnover [XREF_BIBR].
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And USP8 catalyzes ubiquitin removal from both Lys48 linkage and Lys63 linkage polyubiquitination chains.
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71 In contrast to PAR2, USP8 (or AMSH) does not impact CXCR4 ubiquitination but instead modulates the ubiquitin status of ESCRT-0 that is ubiquitinated by the E3 ligase AIP4, 23 reinforcing the idea that ubiquitination of the transport machinery represents an important regulatory event in GPCR trafficking.
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Moreover, P5091 inhibits USP7-, but not USP2- or USP8 mediated cleavage of poly K48 linked ubiquitin chains (visualized by the presence or absence of mono-ubiquitin) (XREF_SUPPLEMENTARY).
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USP8 inhibits Ubiquitin.
| 3
USP8 inhibits Ubiquitin. 3 / 3
| 3
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This zinc-finger ribbon (observed also in USP2, USP8 and USP21 structures) is in the contracted ' closed-hand ' configuration seen in USP8, which was proposed to block ubiquitin access XREF_BIBR.
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In Drosophila melanogaster, UBPY silencing enhanced neurodegenerative TDP-43 phenotypes and the accumulation of insoluble high molecular weight TDP-43 and ubiquitin species.
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This zinc-finger ribbon seems to be in the contracted " closed-hand " configuration seen in USP8 that blocks ubiquitin access (XREF_FIG).
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USP8 affects KDR
| 5
USP8 activates KDR.
| 3
USP8 activates KDR. 3 / 4
| 3
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Perturbed VEGFR2 endosomal trafficking caused by USP8 depletion could modulate endosome linked signal transduction.
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VEGFR2 accumulation also occurred when cells were treated with individual USP8 siRNAs to limit off-target effects.
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VEGFR2 also accumulated in EEA1 positive early endosomes when cells were treated with individual USP8 siRNAs to limit off-target effects.
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USP8 inhibits KDR.
| 1
USP8 inhibits KDR. 1 / 2
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VEGF-A-stimulated VEGFR2 signal transduction is perturbed by USP8 depletion.
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USP8 decreases the amount of KDR.
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USP8 decreases the amount of KDR. 1 / 1
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Accumulation of proteolytic cleavage products in USP8 depleted cells reduced levels of mature VEGFR2 and resulted in lower levels of ubiquitinated full-length receptor.
26459808
RNF41 affects USP8
| 6
RNF41 inhibits USP8.
| 2
RNF41 inhibits USP8. 2 / 3
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When Nrdp1 is increased, more USP8 will be degraded by Nrdp1, and as a return, less USP8 will make Nrdp1 unstable, resulting in less Nrdp1 and more USP8 in the cells.
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RNF41 also negatively regulates the stability of the ubiquitin isopeptidase USP8, a regulator of JAK2 associated cytokine receptor sorting and processing : elevated RNF41 destabilizes the endosomal-sorting-complexes-required-for-transport (ESCRT) -0 complex (Hrs and signal-transducing-and adapter-molecule (STAM) -1 or STAM2), which results in cargo arriving at sorting endosomes being routed to recycling endosomes rather than to lysosomes [XREF_BIBR].
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RNF41 activates USP8.
| 2
RNF41 activates USP8. 2 / 2
| 2
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Since Nrdp1 targets USP8 for ubiquitylation, we speculated that overexpression of Nrdp1 could enhance protein ubiquitylation and USP8 degradation in PC12 cells.
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Nrdp1 activates NRG-1beta-induced HER3 degradation [XREF_BIBR] and USP8 prevents Nrdp1 auto-ubiquitination [XREF_BIBR], with a strong correlation between USP8 expression and Nrdp1 stabilization [XREF_BIBR].
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RNF41 deubiquitinates USP8.
| 1
Modified RNF41 leads to the deubiquitination of USP8. 1 / 1
| 1
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Since Nrdp1 targets USP8 for ubiquitylation, we speculated that overexpression of Nrdp1 could enhance protein ubiquitylation and USP8 degradation in PC12 cells.
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RNF41 decreases the amount of USP8.
| 1
RNF41 decreases the amount of USP8. 1 / 1
| 1
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RNF41 redistributes and ubiquitylates USP8, and reduces USP8 levels.
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USP8 affects PRKN
| 5
USP8 activates PRKN. 5 / 6
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USP8 KD also prevented Parkin KO DA neurons loss and normalized mitochondrial morphological defects, although it did not ameliorate Parkin climbing performance (XREF_FIG).
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Only USP8 supports mitophagy by stabilizing the E3 ligase Parkin.
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H 2 S may upregulate the expression of deubiquitinating enzymes USP8 to antagonize the degradation of Parkin protein.
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In contrast, USP8 promotes parkin mediated mitophagy and thus agonists of this DUB could be developed XREF_BIBR.
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In contrast, USP8 promotes Parkin mediated mitophagy and agonists to USP8 could be developed as potential therapeutics.
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USP8 affects FLIP
| 6
USP8 decreases the amount of FLIP.
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Modified USP8 decreases the amount of FLIP. 3 / 3
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Overexpression of USP8 increased c-FLIP S ubiquitination, decreased FLIP S half-life, decreased FLIP S steady-state levels, and decreased TRAIL resistance (XREF_FIG).
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Over-expression of WT USP8, but not catalytically inactive USP8, increased FLIP S ubiquitination, decreased FLIP S half-life, decreased FLIP S steady-state levels, and decreased TRAIL resistance, while siRNA mediated suppression of USP8 levels had the opposite effects.
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Furthermore, the suppression of FLIP S levels by USP8 over-expression was reversed by introduction of siRNA targeting AIP4.
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USP8 activates FLIP.
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USP8 activates FLIP. 2 / 2
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Loss of PTEN function (right panel, XREF_FIG), in contrast increases pAkt levels, decreases USP8 levels, and turns off the USP8 and AIP4 ubiquitin switch, allowing FLIP S to accumulate and suppress TRAIL induced apoptosis.
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Because PTEN dependent regulation of FLIP S stability is mediated by changes in FLIP S ubiquitination, we took the above USP8 modulated cells, transiently transfected a construct encoding HA tagged ubiquitin, and following FLIP S immunoprecipitation used Western blot analysis to monitor the effect of USP8 alteration on the extent of HA-ubiquitin incorporated into FLIP S.
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USP8 inhibits FLIP.
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USP8 inhibits FLIP. 1 / 1
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Taken together, our data indicate that USP8 functions as a novel deubiquitylase of FLIP L and inhibits extrinsic apoptosis by stabilizing FLIP L.
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EGF affects USP8
| 6
EGF activates USP8.
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EGF activates USP8. 3 / 3
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Collectively, these data demonstrate that the Cbl binding site of the wild-type EGFR and the EGFR-ErbB2 chimera is not required for efficient EGF induced Usp8 tyrosine phosphorylation or coprecipitati[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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EGF treatment induced a faster degradation of EGFR protein in HeLa cells expressing WT USP8 compared to mutants, although EGFR protein levels were comparable in these cells under serum starved conditions (XREF_FIG).
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As we have demonstrated before, deletion of the MIT-domain in Usp8 results in decreased EGF induced Usp8 tyrosine phosphorylation [17].
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EGF activates USP8-C748A. 1 / 1
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pS722 was only found in EGF stimulated cells containing Usp8 C748A, which could indicate that this serine is involved in substrate trapping.
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EGF inhibits USP8.
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EGF inhibits USP8. 2 / 2
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In EGFR-ErbB2 expressing cells, EGF induced Usp8 tyrosine phosphorylation was even lower in the presence of PD153035 than the Usp8 tyrosine phosphorylation level observed in unstimulated and mock trea[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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In cells expressing either EGFR or EGFR-ErbB2, removal of the MIT domain (Usp8 Delta140) resulted in a decrease of the EGF induced Usp8 tyrosine phosphorylation, when compared to Usp8 wt.
21044682
P14_3_3 affects USP8
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P14_3_3 inhibits USP8. 3 / 5
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Another hypothesis is that USP8 is catalytically inhibited in a phosphorylation dependent manner by 14-3-3 proteins during the interphase stage of the cell-cycle, and this regulation is reversed in the M phase [XREF_BIBR].
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Another hypothesis is that USP8 is catalytically inhibited in a phosphorylation-dependent manner by 14-3-3 proteins during the interphase stage of the cell-cycle, and this regulation is reversed in the M phase [ xref ].
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We conclude that UBPY is catalytically inhibited in a phosphorylation-dependent manner by 14-3-3s during the interphase, and this regulation is cancelled in the M phase.
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Hedgehog affects USP8
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Hedgehog activates USP8. 2 / 5
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Mechanistically, we show that Hh promotes the interaction of USP8 with Smo aa625-753, which covers the three PKA and CK1 phosphorylation clusters.
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CFP-Smo was transfected into S2 cells that were treated with GFP dsRNA (control), USP8 dsRNA, or Shi dsRNA and then treated with Hh conditioned medium or control medium.
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USP8 affects autophagy
| 1 3
USP8 activates autophagy.
| 1 2
USP8 activates autophagy. 3 / 4
| 1 2
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We show here that UBPY silencing also activates autophagy in absence of CCCP treatment, which strongly suggests that UBPY is not connected exclusively to mitophagy.
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Inactivation of human UBPY in HeLa cells activates autophagy.
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Lastly, we have shown that shRNA mediated inactivation of UBPY in HeLa cells also affects autophagy which appears to be deregulated with an increased number of autophagosomes and increased autophagy flux.
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USP8 inhibits autophagy.
| 1
USP8 inhibits autophagy. 1 / 1
| 1
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We show here that UBPY silencing also activates autophagy in absence of CCCP treatment, which strongly suggests that UBPY is not connected exclusively to mitophagy.
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USP8 affects SLC22A6
| 1 4
USP8 increases the amount of SLC22A6.
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USP8 increases the amount of SLC22A6. 2 / 2
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In addition, COS-7 cells have fair amount of endogenous USP8, which perhaps have already increased hOAT1 expression and activity to certain extent.
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The protein levels of cell membrane protein marker E-cadherin (XREF_FIG, bottom panel) and cell total protein marker beta-actin (XREF_FIG, bottom panel) were not affected under these conditions, thereby indicating that the change in hOAT1 expression induced by USP8 wild type transfection was not due to the general perturbation of membrane and cellular proteins.
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USP8 inhibits SLC22A6.
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USP8 inhibits SLC22A6. 1 / 1
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In Fig. 10 , USP8 slowed down the rate of hOAT1 degradation as compared to that in control cells ( empty vector-transfected cells ) , suggesting that USP8 played a role in increasing hOAT1 stability .
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USP8 decreases the amount of SLC22A6.
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USP8 decreases the amount of SLC22A6. 1 / 1
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Downexpression of USP8 decreased OAT1 transport activity and OAT1 expression.
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USP8 activates SLC22A6.
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USP8 activates SLC22A6. 1 / 1
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In XREF_FIG, USP8 slowed down the rate of hOAT1 degradation as compared to that in control cells (empty vector transfected cells), suggesting that USP8 played a role in increasing hOAT1 stability.
32818533
AKT affects USP8
| 4
AKT inhibits USP8.
| 1
AKT inhibits USP8. 1 / 2
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In the present study the linkage between PTEN loss, Akt activation, and USP8 levels and activity appeared to be somewhat different, and in our work Akt activation decreased, rather than enhanced, USP8 function by increasing USP8 ubiquitination and decreasing steady-state USP8 levels (data not shown).
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AKT increases the amount of USP8.
| 1
AKT increases the amount of USP8. 1 / 1
| 1
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The AKT kinase has been previously shown to decrease USP8 function by increasing USP8 ubiquitination and decreasing active steady-state USP8 level [XREF_BIBR].
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AKT deubiquitinates USP8.
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AKT leads to the deubiquitination of USP8. 1 / 1
| 1
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The AKT kinase has been previously shown to decrease USP8 function by increasing USP8 ubiquitination and decreasing active steady-state USP8 level [XREF_BIBR].
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AKT activates USP8.
| 1
AKT activates USP8. 1 / 1
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In addition to suppressing levels of USP8, Akt may also stimulate the activity of USP8 toward select targets such as Nrdp1.
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USP8 affects LRIG1
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USP8 activates LRIG1. 4 / 4
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These results suggest that simultaneous blockage of USP8 may further enhance LRIG1 dependent Met degradation and subsequent tumor growth inhibition by SAIT301 and other Met targeting drugs that have a similar mechanism of action.
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Over-expression of USP8 substantially reduced the LRIG1 degradation (XREF_FIG).
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Moreover, we showed that suppression of USP8 activity, by over-expression of USP8-CS, led to enhancement of the anti-tumor activity of Met targeting therapeutic antibody by promoting degradation of both Met and LRIG1.
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This result suggests that SAIT301 perturbs USP8 mediated modulation of LRIG1, resulting in the degradation of LRIG1.
24828152
USP8 affects Hedgehog
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USP8 activates Hedgehog. 2 / 4
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Loss of USP8/UBPY blocked Hh-induced Smo accumulation whereas overexpression of USP8/UBPY resulted in ectopic Smo accumulation and Hh pathway activation [42,43].
| PMC
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Although the loss-of-function of USP8 can block Hh induced cell surface accumulation of Smo, we found that USP8 only stabilizes Smo but does not regulate Smo phosphorylation in the absence of Hh (XREF_FIG), suggesting that the regulation of Smo by USP8 is downstream of Smo phosphorylation.
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USP8 affects localization
| 4
USP8 inhibits localization.
| 2
USP8 inhibits localization. 2 / 2
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Moreover, we found that USP8 prevents Smo localization to early endosomes that are labeled with Rab5.
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USP8 Prevents the Localization of Smo to the Early Endosome.
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USP8 activates localization.
| 2
USP8 activates localization. 2 / 2
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Moreover, Shi RNAi attenuated the localization of Smo in the early endosomes (XREF_FIG), whereas USP8 RNAi elevated the localization (XREF_FIG).
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Catalytic inactivation of USP8 incurs EGFR hyperubiquitination and promotes receptor localization to endosomes marked by high ubiquitin content.
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USP8 affects STAM2
| 4
USP8 decreases the amount of STAM2.
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USP8 decreases the amount of STAM2. 2 / 2
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siRNAs USP8 (B) and (C) reduced expression of MET and STAM2.
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UBPy deficient cells exhibit aberrantly enlarged early endosomes colocalizing with enhanced ubiquitination and have reduced levels of HRS and STAM2.
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USP8 activates STAM2.
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USP8 activates STAM2. 2 / 2
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Hence, locally recruited UBPY might aid the displacement of STAM2 from HD-PTP.
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These binding reactions provide a scenario in which UBPY could aid transit of EGFR to ESCRT-III by helping to displace STAM2 from HD-PTP.
23477725
USP8 affects AKT
| 4
USP8 activates AKT.
| 2
USP8 activates AKT. 2 / 2
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USP8 activity thus modulates VEGF-A-stimulated Akt and ERK1/2 activation but does not affect other VEGFR2 associated signal transduction pathways.
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Importantly, knockdown of USP8 inhibited activation of the Akt signaling pathway by decreasing the phosphorylation level of Akt and up-regulated p53 expression, while USP8 overexpression increased activation of the Akt signaling pathway in Hucct-1 cells.
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USP8 inhibits AKT.
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USP8 inhibits AKT. 1 / 1
| 1
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Whereas ERK1/2 and Akt signaling is inhibited by USP8 depletion, other signal transduction pathways are unaffected.
26459808
USP8 decreases the amount of AKT.
| 1
USP8 decreases the amount of AKT. 1 / 1
| 1
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Importantly, knockdown of USP8 inhibited activation of the Akt signaling pathway by decreasing the phosphorylation level of Akt and up-regulated p53 expression, while USP8 overexpression increased activation of the Akt signaling pathway in Hucct-1 cells.
32273758
USP8 inhibits cell differentiation.
| 3
Mutated USP8 inhibits cell differentiation. 1 / 1
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USP8 overexpression blocked NGF induced neurites outgrowth while the overexpression of the catalytically inactive mutant USP8 and UBPy (C748A) caused a marked increase of cell differentiation.
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USP8-C748A inhibits cell differentiation. 1 / 1
| 1
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USP8 overexpression blocked NGF induced neurites outgrowth while the overexpression of the catalytically inactive mutant USP8 and UBPy (C748A) caused a marked increase of cell differentiation.
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USP8 bound to NTRK1 inhibits cell differentiation. 1 / 1
| 1
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The deubiquitinating enzyme UBPy and USP8 interacts with TrkA and inhibits neuronal differentiation in PC12 cells.
25662281
USP8 activates cell differentiation.
| 1
reach
Here, we provide mechanistic evidence indicating that ubiquitin carboxyl-terminal hydrolase 8 (USP8) modulates BDNF and TrkB dependent neuronal differentiation.
33288548
USP8 affects TNFSF10
| 3
Modified USP8 inhibits TNFSF10. 3 / 3
| 3
reach
Over-expression of WT USP8, but not catalytically inactive USP8, increased FLIP S ubiquitination, decreased FLIP S half-life, decreased FLIP S steady-state levels, and decreased TRAIL resistance, while siRNA mediated suppression of USP8 levels had the opposite effects.
20484045
reach
Overexpression of USP8 increased c-FLIP S ubiquitination, decreased FLIP S half-life, decreased FLIP S steady-state levels, and decreased TRAIL resistance (XREF_FIG).
22348197
reach
Overexpression of USP8 increased c-FLIP S ubiquitination, decreased c-FLIP S half-life, decreased c-FLIP S steady-state levels, and decreased TRAIL resistance.
23070002
USP8 affects ENaC
| 3
USP8 activates ENaC. 3 / 3
| 3
reach
USP8 increased ENaC current in Xenopus oocytes and collecting duct epithelia and enhanced ENaC abundance at the cell surface in HEK 293 cells.
23297398
reach
Thus, USP8 and USP2-45 selectively modulate ENaC trafficking at different steps in the endocytic pathway.
23297398
reach
This resulted from altered endocytic sorting; USP8 abolished ENaC degradation in the endocytic pathway, but it had no effect on ENaC endocytosis.
23297398
OTUB1 affects USP8
| 1 2
OTUB1 inhibits USP8. 3 / 3
| 1 2
sparser
This unexpected function of otubain-1 might be mediated through the inhibition of USP8, a DUB that binds to and deubiquitylates GRAIL; however, it is not known how otubain-1 might inhibit USP8 (Ref. xref ).
18535581
reach
This unexpected function of otubain-1 might be mediated through the inhibition of USP8, a DUB that binds to and deubiquitylates GRAIL; however, it is not known how otubain-1 might inhibit USP8.
18535581
reach
Interestingly, Otub1 expression completely abolished USP8 mediated stabilization of GRAIL when all 3 proteins were co-expressed.
21078124
USP8 affects sub
| 3
USP8 activates sub. 2 / 2
| 2
reach
These data suggest that USP8 phosphorylation, possibly on Tyr residue (s), enhances its DUB activity.
29472535
reach
The putative substrate of BRUCE could be USP8 and if this is the case, ubiquitination of USP8 by BRUCE is expected to enhance its Dub activity over Ub-BRIT1, thereby facilitating removal of the Ub chains from K63-Ub-BRIT1 and promoting recruitment of de-ubiquitinated BRIT1 to sites of DNA damage.
26683461
USP8-S680A activates sub. 1 / 1
| 1
reach
Furthermore, the catalytic activity of USP8 is inhibited by phosphorylation on Ser 680, based on the fact that the S680A mutant of USP8 exhibites enhanced DUB activity toward polyubiquitin chains and EGFR.
21480003
USP8 affects protein
| 3
USP8 activates protein.
| 2
USP8 activates protein. 2 / 2
| 2
eidos
Altogether , RNAi for UBR4 , HGS , STAM , and USP8 led to the upregulation of 672 proteins and to the downregulation of 797 proteins , compared to a control RNAi ( white RNAi ) .
33658508
eidos
Overall , there were 15 proteins that were similarly upregulated by RNAi for UBR4 , STAM , HGS , and USP8 , compared to a control RNAi .
33658508
USP8 inhibits protein.
| 1
USP8 inhibits protein. 1 / 1
| 1
eidos
Altogether , RNAi for UBR4 , HGS , STAM , and USP8 led to the upregulation of 672 proteins and to the downregulation of 797 proteins , compared to a control RNAi ( white RNAi ) .
33658508
USP8 affects gefitinib
| 3
USP8 activates gefitinib.
| 2
USP8 activates gefitinib. 2 / 2
| 2
reach
Interestingly, the inhibition of USP8 suppresses growth of gefitinib resistant non small cell lung cancer cells, though no link to the potential impact on HIF-1alpha is reported.
27014628
reach
Silencing or pharmacological inhibition of USP8 deubiquitinase, relevant in particular to the stability of RTKs such as EGFR and MET, was shown to induce death of gefitinib resistant NSCLC cells in vitro and in vivo [XREF_BIBR].
24722523
USP8 inhibits gefitinib.
| 1
USP8 inhibits gefitinib. 1 / 1
| 1
reach
Knock-down of USP8 selectively decreases viability of gefitinib resistant NSCLC cells.
23748694
USP8 affects dopamine
| 3
USP8 activates dopamine.
| 2
USP8 activates dopamine. 2 / 2
| 2
reach
USP8 down-regulation completely prevented the loss of PINK1 KO DA neurons (XREF_FIG), restoring dopamine to wild-type levels (XREF_FIG).
30988163
reach
USP8 KD also prevented Parkin KO DA neurons loss and normalized mitochondrial morphological defects, although it did not ameliorate Parkin climbing performance (XREF_FIG).
30988163
USP8 decreases the amount of dopamine.
| 1
USP8 decreases the amount of dopamine. 1 / 1
| 1
reach
Heterozygous USP8 gene deletion (USP8 -/+) in PINK1 KO background also completely prevented the loss of DA neurons (XREF_FIG), restored dopamine levels to wild-type (XREF_FIG), corrected thoracic muscle fiber disorganization (XREF_FIG) and mitochondrial structure (XREF_FIG), ameliorated the shorter longevity (XREF_FIG), and completely corrected the locomotor defects (XREF_FIG).
30988163
USP8 affects cilium assembly
| 1 2
USP8 activates cilium assembly.
| 2
USP8 activates cilium assembly. 2 / 2
| 2
reach
KD of the EGF receptor (EGFR) in human RPE cells inhibits USP8 Tyr717 and Tyr810 phosphorylation, which enables TCHP and AURKA degradation and reverses the serum-induced effects on ciliogenesis and cell proliferation [50].
| PMC
reach
In zebrafish, knockout (KO) of kctd17 impairs ciliogenesis in Kupffer’s vesicle and induces situs inversus [74], whereas KO of usp8 increases ciliogenesis in the pronephric duct and causes renal cysts [50].
| PMC
USP8 inhibits cilium assembly.
| 1
USP8 inhibits cilium assembly. 1 / 1
| 1
eidos
CRL3KCTD17 , USP8 , and TCHP TCHP , a centriolar protein originally identified as a keratin-binding protein , activates AURKA and suppresses ciliogenesis [ 101,141,142 ] .
| PMC
USP8 affects PINK1
| 3
USP8 activates PINK1. 2 / 2
| 2
reach
USP8 down-regulation completely prevented the loss of PINK1 KO DA neurons (XREF_FIG), restoring dopamine to wild-type levels (XREF_FIG).
30988163
reach
USP8 down-regulation rescues mitochondria defects of PINK1 KO flies.
30988163
USP8 activates mutated PINK1. 1 / 1
| 1
reach
Both USP8 fly lines (USP8 +/- and USP8 RNAi) restored complex I activity of PINK1 mutants (XREF_FIG).
30988163
USP8 affects MET
| 2
USP8 decreases the amount of MET.
| 1
USP8 decreases the amount of MET. 1 / 2
| 1
reach
Ubiquitinated LRIG1 recruits c-Met to lysosomes for degradation; reduction in LRIG1 ubiquitination by USP8 depletion or inactivation thus enables c-Met levels and functionality to be maintained.
29543760
USP8 increases the amount of MET.
| 1
USP8 increases the amount of MET. 1 / 1
| 1
reach
We further found that USP8 inhibition decreased levels of multiple receptor tyrosine kinases (RTKs) by ~ 90%, such as epidermal growth factor receptor (EGFR) and c-Met.
34081623
USP8 affects ERBB2
| 3
USP8 inhibits ERBB2.
| 2
USP8 inhibits ERBB2. 2 / 2
| 2
reach
The USP8 inhibited HER-2 positive GC cell proliferation and migration in vivo and in vitro and probably served as a novel potential therapeutic biomarker for HER-2 positive GC.
33116578
reach
USP8 Inhibitor Suppresses HER-2 Positive Gastric Cancer Cell Proliferation and Metastasis via the PI3K and AKT Signaling Pathway.
33116578
USP8 increases the amount of ERBB2.
| 1
USP8 increases the amount of ERBB2. 1 / 1
| 1
reach
Western blotting confirmed that knockdown of USP8 not only reduced RTK phosphorylation, but also the total levels of EGFR, ERBB2, ERBB3, and MET in H1975 and H1650 cells (XREF_FIG).
23748694
USP8 affects CCR7
| 1 2
USP8 inhibits CCR7.
| 1 1
USP8 inhibits CCR7. 2 / 2
| 1 1
reach
Inhibiting USP8 leads to decrease in IL-7ra mRNA as well as Ccr7 [81].
31208841
eidos
Inhibiting USP8 leads to decrease in IL-7ra mRNA as well as Ccr7 [ 81 ] .
31208841
USP8 activates CCR7.
| 1
USP8 activates CCR7. 1 / 1
| 1
reach
Inhibiting USP8 leads to decrease in IL-7ra mRNA as well as Ccr7 [XREF_BIBR].
31208841
USP8 affects AURKA
| 1 2
USP8 activates AURKA.
| 1 1
USP8 activates AURKA. 2 / 2
| 1 1
reach
KD of the EGF receptor (EGFR) in human RPE cells inhibits USP8 Tyr717 and Tyr810 phosphorylation, which enables TCHP and AURKA degradation and reverses the serum-induced effects on ciliogenesis and cell proliferation [50].
| PMC
eidos
CRL3KCTD17 , USP8 , and TCHP TCHP , a centriolar protein originally identified as a keratin-binding protein , activates AURKA and suppresses ciliogenesis [ 101,141,142 ] .
| PMC
USP8 inhibits AURKA.
| 1
USP8 inhibits AURKA. 1 / 1
| 1
reach
KD of the EGF receptor (EGFR) in human RPE cells inhibits USP8 Tyr717 and Tyr810 phosphorylation, which enables TCHP and AURKA degradation and reverses the serum-induced effects on ciliogenesis and cell proliferation [50].
| PMC
Luteolin affects USP8
| 3
Luteolin inhibits USP8.
| 1
Luteolin inhibits USP8. 1 / 1
| 1
reach
Taken together, our findings suggested that luteolin inhibits microglial inflammation by enhancing USP8 protein production.
24861766
Luteolin increases the amount of USP8.
| 1
Luteolin increases the amount of USP8. 1 / 1
| 1
reach
Western blot analysis verified that USP8 expression is upregulated by luteolin.
24861766
Luteolin decreases the amount of USP8.
| 1
Luteolin decreases the amount of USP8. 1 / 1
| 1
reach
We next hypothesized that luteolin inhibits microglial inflammation by regulating USP8 gene expression.
24861766
USP8 affects BAX
| 3
USP8 inhibits BAX.
| 1
USP8 inhibits BAX. 1 / 1
| 1
reach
Moreover, silencing of USP8 also promoted apoptosis in cholangiocarcinoma cells by regulating the Bcl-2 and Bax axis and Caspase cascade; up-regulation of USP8 decreased apoptosis in Hucct-1 cells.
32273758
USP8 increases the amount of BAX.
| 1
USP8 increases the amount of BAX. 1 / 1
| 1
reach
The results of western blot indicated that knockdown of USP8 down-regulated the expression of Cyclin D1, CDK4, CDK6, p-AKT, and Bcl2, and up-regulated the expression of Bax.
33293867
USP8 decreases the amount of BAX.
| 1
USP8 decreases the amount of BAX. 1 / 1
| 1
reach
The results of western blot indicated that knockdown of USP8 down-regulated the expression of Cyclin D1, CDK4, CDK6, p-AKT, and Bcl2, and up-regulated the expression of Bax.
33293867
Indometacin affects USP8
2 |
Indometacin decreases the amount of USP8. 2 / 2
2 |
ctd
No evidence text available
28201806
ctd
No evidence text available
28628672
Hsa-miR-95-5p affects USP8
2 |
Hsa-miR-95-5p decreases the amount of USP8. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
20371350
biopax:mirtarbase
No evidence text available
23446348
Hsa-miR-4789-3p affects USP8
2 |
Hsa-miR-4789-3p decreases the amount of USP8. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
23446348
biopax:mirtarbase
No evidence text available
20371350
Hsa-miR-466 affects USP8
2 |
Hsa-miR-466 decreases the amount of USP8. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
23446348
biopax:mirtarbase
No evidence text available
20371350
Hsa-miR-4643 affects USP8
2 |
Hsa-miR-4643 decreases the amount of USP8. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
23446348
biopax:mirtarbase
No evidence text available
20371350
Hsa-miR-19b-3p affects USP8
2 |
Hsa-miR-19b-3p decreases the amount of USP8. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
23446348
biopax:mirtarbase
No evidence text available
20371350
Hsa-miR-19a-3p affects USP8
2 |
Hsa-miR-19a-3p decreases the amount of USP8. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
23446348
biopax:mirtarbase
No evidence text available
20371350
Bisphenol A affects USP8
2 |
Bisphenol A increases the amount of USP8. 2 / 2
2 |
ctd
No evidence text available
25181051
ctd
No evidence text available
30816183
USP8 affects mitophagy
| 2
USP8 activates mitophagy. 2 / 2
| 2
eidos
USP8 promotes Parkin-mediated mitophagy by deubiquitinating Parkin and promoting its recruitment to the mitochondria .
30126257
eidos
Usp8 knockdown impairs Parkin-mediated mitophagy by preventing Parkin recruitment of depolarized mitochondria .
30126257
USP8 affects lipopolysaccharide
| 2
reach
USP8 overexpression also reduced the production of lipopolysaccharide (LPS)-induced proinflammatory mediators such as inducible nitric oxide synthase (iNOS), nitric oxide (NO), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2).
24861766
reach
USP8 overexpression also reduced the production of lipopolysaccharide (LPS)-induced proinflammatory mediators such as inducible nitric oxide synthase (iNOS), nitric oxide (NO), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2).
24861766
reach
The present study is the first, to the best of our knowledge, to investigate the effects of ubiquitin specific peptidase 8 (USP8) on IHR induced inflammation in renal tubular epithelial cells and examine the underlying mechanism.
30221684
reach
Effect of deubiquitinase USP8 on hypoxia and reoxygenation induced inflammation by deubiquitination of TAK1 in renal tubular epithelial cells.
30221684
USP8 affects Wnt
| 2
USP8 activates Wnt. 2 / 2
| 2
reach
Additionally, the deubiquitinating enzymes UBPY and USP6 may promote the recycling of endocytosed FZD back to the surface and restore Wnt signaling.
29632210
reach
USP8 and UBPY is reported to activate the Wnt and beta-catenin pathway by targeting Frizzled G protein coupled protein XREF_BIBR.
26883469
USP8 affects TARDBP
| 2
USP8 inhibits TARDBP. 2 / 2
| 2
reach
In Drosophila melanogaster, UBPY silencing enhanced neurodegenerative TDP-43 phenotypes and the accumulation of insoluble high molecular weight TDP-43 and ubiquitin species.
24825905
reach
Furthermore, knockdown of UBPY promotes formation of insoluble TDP-43 aggregates and induced neurotoxicity in D. melanogaster.
27693252
USP8 inhibits Neoplasm Metastasis. 2 / 2
| 2
reach
USP8 Inhibitor Suppresses HER-2 Positive Gastric Cancer Cell Proliferation and Metastasis via the PI3K and AKT Signaling Pathway.
33116578
reach
XREF_BIBR, XREF_BIBR Therefore, it can be inferred that down-regulation of USP8 may inhibit the proliferation and even metastasis of GC through this pathway.
32848421
USP8 affects IL7R
| 2
USP8 activates IL7R. 2 / 2
| 2
reach
Inhibiting USP8 leads to decrease in IL-7ra mRNA as well as Ccr7 [XREF_BIBR].
31208841
reach
Inhibiting USP8 leads to decrease in IL-7ra mRNA as well as Ccr7 [81].
31208841
USP8 affects HAT1
| 1 1
USP8 inhibits HAT1. 2 / 2
| 1 1
reach
Interestingly, HAT1 is upregulated also by USP8 loss but it is not regulated by RNAi for HGS, STAM.
33658508
eidos
Interestingly , HAT1 is upregulated also by USP8 loss but it is not regulated by RNAi for HGS , STAM .
33658508
USP8 affects EPS15
| 2
USP8 activates EPS15. 2 / 2
| 2
reach
Another DUB enzyme, USP8, functions similarly to target Eps15 [XREF_BIBR].
29543760
reach
Furthermore, inactivation of UBPY caused the accumulation of Eps15 on the endosomal aggregates.
16771824
USP8 affects EGF
| 2
USP8 activates EGF. 2 / 2
| 2
reach
Cleavage of USP8 led to increased deubiqutination of the EGF receptor, impairing its downregulation and sustaining EGF signaling.
25485838
reach
XREF_BIBR Cleavage of USP8 led to increased deubiquitination of the epidermal growth factor receptor (EGFR), impairing its downregulation and sustaining EGF signaling.
32848421
USP8 affects Death
| 2
USP8 activates Death. 2 / 2
| 2
reach
Silencing or pharmacological inhibition of USP8 deubiquitinase, relevant in particular to the stability of RTKs such as EGFR and MET, was shown to induce death of gefitinib resistant NSCLC cells in vitro and in vivo [XREF_BIBR].
24722523
reach
USP8 siRNAs reduced viability and increased death in cSCC lines but had little effect in normal skin cells (XREF_FIG a).
31705877
USP8 affects Cell Survival
| 2
USP8 activates Cell Survival. 2 / 2
| 2
reach
USP8 inhibition markedly reduced cell viability in gefitinib resistant and -sensitive NSCLC cells, but exhibited no observable effects on normal control cells (XREF_FIG).
23748694
reach
H1975 and H1650 transfected with si-USP8 showed a dramatic decrease in cell viability compared to mock transfected cells, indicating that the suppression of USP8 effectively decreases NSCLC cell viability (XREF_FIG and XREF_SUPPLEMENTARY).
23748694
reach
Indeed, inhibition of USP8 either by its knockdown or synthetic small molecule led to attenuation of variety of receptor tyrosine kinase (RTK) activities, resulting in the inhibition of cell proliferation in gefitinib-resistant and -sensitive non-small cell lung cancer (NSCLC) cells [47] .
26077642
USP8 affects BACE1
| 2
USP8 decreases the amount of BACE1. 2 / 2
| 2
reach
Studies have shown that RNAi mediated depletion of USP8 increased BACE1 ubiquitination on Lys 501, promoted BACE1 accumulation in the early endosomes and late endosomes and lysosomes, and decreased levels of BACE1 in the recycling endosomes.
28469554
reach
Moreover, USP8 depletion increased BACE1 ubiquitination, promoted BACE1 accumulation in the early endosomes and late endosomes and lysosomes, and decreased levels of BACE1 in the recycling endosomes.
27302062
USP8 affects Ala-Gly-Ser
| 2
USP8 inhibits Ala-Gly-Ser. 2 / 2
| 2
reach
Therefore, we found that down-regulation of USP8 could significantly inhibit the cell-cycle of AGS and block the G1 phase.
32848421
reach
Therefore, it was confirmed that down-regulation of USP8 could inhibit the proliferation of NCI-N87, MKN-45 and AGS cell lines, which is HER-3 positive GC cells.
32848421
CHMP1B affects USP8
| 2
CHMP1B activates USP8. 2 / 2
| 2
reach
Furthermore, the finding that CHMP1B is a target of USP8 may shed new light in the future on understanding its contribution to membrane receptor trafficking, resistance to chemotherapy or EGFR stabilization in Cushing 's disease.
29933386
reach
CHMP1B is a target of USP8 and UBPY regulated by ubiquitin during endocytosis.
29933386
Sodium arsenate affects USP8
2 |
Sodium arsenate increases the amount of USP8.
1 |
Sodium arsenate increases the amount of USP8. 1 / 1
1 |
ctd
No evidence text available
21795629
Sodium arsenate decreases the amount of USP8.
1 |
Sodium arsenate decreases the amount of USP8. 1 / 1
1 |
ctd
No evidence text available
21795629
Ubiquitin affects USP8
| 2
Ubiquitin inhibits USP8.
| 1
Ubiquitin inhibits USP8. 1 / 1
| 1
reach
These data indicate that under ischemic conditions, Nrdp1 upregulation may hinder the stabilization of HIF-1alpha in neurons via promoting ubiquitin mediated degradation of USP8, thus attenuating cellular adaptive response to hypoxia and ischemia.
28979191
Ubiquitin activates USP8.
| 1
Ubiquitin activates USP8. 1 / 1
| 1
reach
Nbr1 binds additionally to proteins implicated in ubiquitin mediated protein turnover and vesicle trafficking : ubiquitin specific peptidases USP8, and the endosomal transport regulator p14 and Robld3.
19427866
USP8 inhibits signal transduction.
| 1
USP8 inhibits signal transduction. 1 / 1
| 1
reach
VEGF-A-stimulated VEGFR2 signal transduction is perturbed by USP8 depletion.
26459808
USP8 activates signal transduction.
| 1
reach
The inhibition of USP8 downregulated the Notch signalling pathway via NICD destabilization, resulting in the retardation of cellular growth, wound closure, and colony forming ability of breast cancer cell lines.
31527799
USP8 affects ptc
| 2
USP8 increases the amount of ptc. 1 / 1
| 1
reach
The catalytic domain of USP8 (USP8NT3) was sufficient to reduce Smo ubiquitination (XREF_FIG, lane 4, top panel), enhance the accumulation of endogenous Smo (XREF_FIG), and increase the GFP-Smo-mediated induction of ectopic dpp-lacZ and ptc expression (XREF_FIG, XREF_SUPPLEMENTARY '' ').
22253573
Modified USP8 increases the amount of ptc. 1 / 1
| 1
reach
Co-expression of Flag-USP8 with GFP-Smo by MS1096 Gal4 caused induction of dpp-lacZ and ptc expression in A-compartment cells both close to and away from the A/P boundary (XREF_FIG), whereas the expression of Flag-USP8 alone did not induce ectopic dpp-lacZ and ptc expression (XREF_FIG).
22253573
USP8 affects cell cycle
| 2
USP8 inhibits cell cycle.
| 1
USP8 inhibits cell cycle. 1 / 1
| 1
reach
Knockdown of USP8 inhibited the proliferation, migration, invasion, and cell cycle progression of A549 and H1299 cells, and promoted the apoptosis.
33293867
USP8 activates cell cycle.
| 1
USP8 activates cell cycle. 1 / 1
| 1
reach
These data clearly indicate that USP8 depletion induces the loss of trichoplein and causes the ciliogenesis dependent cell cycle arrest.
29472535
USP8 affects TCHP
| 2
USP8 inhibits TCHP.
| 1
USP8 inhibits TCHP. 1 / 1
| 1
reach
KD of the EGF receptor (EGFR) in human RPE cells inhibits USP8 Tyr717 and Tyr810 phosphorylation, which enables TCHP and AURKA degradation and reverses the serum-induced effects on ciliogenesis and cell proliferation [50].
| PMC
USP8 activates TCHP.
| 1
USP8 activates TCHP. 1 / 1
| 1
reach
KD of the EGF receptor (EGFR) in human RPE cells inhibits USP8 Tyr717 and Tyr810 phosphorylation, which enables TCHP and AURKA degradation and reverses the serum-induced effects on ciliogenesis and cell proliferation [50].
| PMC
USP8 affects NRG
| 2
USP8 increases the amount of NRG.
| 1
USP8 increases the amount of NRG. 1 / 1
| 1
reach
Mechanistically, we found that USP8 increased the expression of neuregulin receptor degradation protein-1 (Nrdp1), potently downregulated the expression of TLR4 and myeloid differentiation primary response protein 88 (MyD88) protein, and inhibited the phosphorylation of IkappaB kinase (IKK) beta and kappa B-alpha (IkappaBalpha), thereby reducing nuclear translocation of p65 by inhibiting the activation of the nuclear factor-kappaB (NF-kappaB) signaling pathway in LPS induced mice.
32335193
USP8 activates NRG.
| 1
USP8 activates NRG. 1 / 1
| 1
reach
Researchers have found that USP8 markedly enhanced the stability of neuregulin receptor degradation protein-1 (Nrdp1), which in turn inhibited the production of proinflammatory cytokines in toll like receptor triggered macrophages.
24861766
USP8 affects HIF1A
| 2
USP8 inhibits HIF1A.
| 1
USP8 inhibits HIF1A. 1 / 1
| 1
reach
This de-ubiquitination activity has made USP8 a stabilizing molecule for HIF-1alpha protein, in which USP8 prevents HIF-1alpha from pVHL mediated degradation.
28979191
USP8 activates HIF1A.
| 1
USP8 activates HIF1A. 1 / 1
| 1
reach
These data suggest that Nrdp1 may attenuate neuron 's adaptive response to hypoxia and ischemia via interfering USP8 mediated HIF-1alpha stabilization, thus contributing to neuronal death under ischemic conditions.
28979191
USP8 affects HGS
| 2
USP8 decreases the amount of HGS. 1 / 1
| 1
reach
UBPy deficient cells exhibit aberrantly enlarged early endosomes colocalizing with enhanced ubiquitination and have reduced levels of HRS and STAM2.
17452457
Modified USP8 decreases the amount of HGS. 1 / 1
| 1
reach
Similarly, the overexpression of Ubpy can also rescue the loss of Hrs in mop knockdown by removing the ubiquitin moiety from Hrs.
26224310
USP8 affects ERK
| 2
USP8 inhibits ERK.
| 1
USP8 inhibits ERK. 1 / 1
| 1
reach
Whereas ERK1/2 and Akt signaling is inhibited by USP8 depletion, other signal transduction pathways are unaffected.
26459808
USP8 activates ERK.
| 1
USP8 activates ERK. 1 / 1
| 1
reach
USP8 activity thus modulates VEGF-A-stimulated Akt and ERK1/2 activation but does not affect other VEGFR2 associated signal transduction pathways.
26459808
USP8 affects CLOCK
| 2
USP8 inhibits CLOCK.
| 1
USP8 inhibits CLOCK. 1 / 1
| 1
reach
In Drosophila, USP8 was recently reported to decrease CLK activity by deubiquitylation XREF_BIBR.
24013921
USP8 decreases the amount of CLOCK.
| 1
USP8 decreases the amount of CLOCK. 1 / 1
| 1
reach
CLOCK deubiquitylation by USP8 inhibits CLK and CYC transcription in Drosophila.
23154984
USP8 affects BDNF
| 2
USP8 increases the amount of BDNF.
| 1
USP8 increases the amount of BDNF. 1 / 1
| 1
reach
Moreover, USP8 protein regulates the differentiation and proper BDNF dependent dendritic formation of hippocampal neurons in vitro and in vivo We conclude that USP8 positively regulates the levels and activation of TrkB modulating BDNF dependent neuronal differentiation.
33288548
USP8 activates BDNF.
| 1
USP8 activates BDNF. 1 / 1
| 1
reach
Here, we provide mechanistic evidence indicating that ubiquitin carboxyl-terminal hydrolase 8 (USP8) modulates BDNF and TrkB dependent neuronal differentiation.
33288548
PTEN affects USP8
| 2
PTEN increases the amount of USP8. 1 / 1
| 1
reach
Loss of PTEN function (right panel, XREF_FIG), in contrast increases pAkt levels, decreases USP8 levels, and turns off the USP8 and AIP4 ubiquitin switch, allowing FLIP S to accumulate and suppress TRAIL induced apoptosis.
20484045
Mutated PTEN increases the amount of USP8. 1 / 1
| 1
reach
Conversely, exposure of PTEN mutant human GBM cells to an Akt inhibitor enhanced USP8 levels (last lane, XREF_FIG).
20484045
LEP affects USP8
| 1 1
LEP increases the amount of USP8.
| 1
LEP increases the amount of USP8. 1 / 1
| 1
reach
Bland and colleagues suggested that leptin increases the expression of USP8, which in turn deubiquitylates the leptin receptor by cleaving Lys48-ubiquitin chains, among other (still unknown) chain types.
33483467
LEP activates USP8.
| 1
LEP activates USP8. 1 / 1
| 1
eidos
Bland and colleagues suggested that leptin increases the expression of USP8 , which in turn deubiquitylates the leptin receptor by cleaving Lys48-ubiquitin chains , among other ( still unknown ) chain types .
33483467
KDR affects USP8
| 2
KDR inhibits USP8.
| 1
KDR inhibits USP8. 1 / 1
| 1
reach
Quantification of immunoblot data showed that whereas ligand stimulated VEGFR2 ubiquitination displayed a characteristic peak and decline, under conditions of USP8 depletion VEGFR2 ubiquitination persisted.
26459808
KDR activates USP8.
| 1
KDR activates USP8. 1 / 1
| 1
reach
Quantification of VEGFR2 residing in the endosome-lysosome system upon CHX treatment revealed VEGFR2 levels were 30% higher in non stimulated, USP8 depleted cells.
26459808
GST affects USP8
| 1 1
GST inhibits USP8.
| 1
GST inhibits USP8. 1 / 1
| 1
reach
The fused GST might perturb the regulatory mechanism of USP8.
29472535
GST activates USP8.
| 1
GST activates USP8. 1 / 1
| 1
sparser
Importantly, GST-EGFR phosphorylated non-tagged USP8 and elevated its DUB activity toward ubiquitin oligomers (Fig.  xref ; lanes 1–3), but GST-EGFR did not activate GST-USP8 (Supplementary Fig.  xref ).
29472535
14-3-3epsilon affects USP8
| 2
14-3-3epsilon inhibits USP8. 1 / 1
| 1
reach
Addition of GST-14-3-3epsilon dose-dependently inhibited the activity of wild-type UBPY as judged by the increased and decreased levels of Ub chains (especially Ub 4-7) and Ub monomer (Ub 1), respecti[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
17720156
14-3-3epsilon inhibits USP8-S680A. 1 / 1
| 1
reach
By contrast, GST-14-3-3epsilon did not inhibit the activity of UBPY S680A which does not interact with 14-3-3s.
17720156
Tungsten affects USP8
1 |
Tungsten decreases the amount of USP8. 1 / 1
1 |
ctd
No evidence text available
30912803
Toluene 2,4-diisocyanate decreases the amount of USP8. 1 / 1
1 |
ctd
No evidence text available
11379042
Titanium dioxide affects USP8
1 |
Titanium dioxide increases the amount of USP8. 1 / 1
1 |
ctd
No evidence text available
23409001
Tetrachloromethane affects USP8
1 |
Tetrachloromethane decreases the amount of USP8. 1 / 1
1 |
ctd
No evidence text available
31150632
Sodium arsenite affects USP8
1 |
Sodium arsenite increases the amount of USP8. 1 / 1
1 |
ctd
No evidence text available
12016162
Schizandrin B affects USP8
1 |
Schizandrin B decreases the amount of USP8. 1 / 1
1 |
ctd
No evidence text available
31150632
Phorbol 13-acetate 12-myristate decreases the amount of USP8. 1 / 1
1 |
ctd
No evidence text available
25613284
Oleic acid affects USP8
| 1
Oleic acid inhibits USP8. 1 / 1
| 1
reach
Dithiothreitol, a reducing agent that reverses sulfhydration mediated covalent modification, increased the ubiquitylation level of parkin, abolished the effects of exogenous H 2 S on USP8 deubiquitylation and suppressed the interaction of USP8 with parkin in neonatal rat cardiomyocytes treated with high glucose, oleate and palmitate.
32257541
Nonanoic acid affects USP8
1 |
Nonanoic acid increases the amount of USP8. 1 / 1
1 |
ctd
No evidence text available
11379042
Nocodazole affects USP8
| 1
Nocodazole activates USP8. 1 / 1
| 1
reach
HeLa cells transfected with FLAG-UBPY were treated with or without nocodazole, and FLAG-UBPY was immunopurified from their lysates in the same way as in Fig. 3.
17720156
Nickel monoxide affects USP8
1 |
Nickel monoxide increases the amount of USP8. 1 / 1
1 |
ctd
No evidence text available
19167457
Methyltestosterone affects USP8
1 |
Methyltestosterone decreases the amount of USP8. 1 / 1
1 |
ctd
No evidence text available
29191790
Methyl methanesulfonate increases the amount of USP8. 1 / 1
1 |
ctd
No evidence text available
23649840
Methapyrilene affects USP8
1 |
Methapyrilene decreases the amount of USP8. 1 / 1
1 |
ctd
No evidence text available
30467583
Lenalidomide affects USP8
| 1
Lenalidomide increases the amount of USP8. 1 / 1
| 1
reach
In addition to diminishing RNF41 auto-ubiquitination, which results in increased RNF41 expression, lenalidomide treatment increased USP8 expression and basal expression and signaling of EpoR and interleukin-3 receptors, without altering expression of Type II receptors such as c-Kit and IFNAR.
27197154
Jinfukang affects USP8
1 |
Jinfukang decreases the amount of USP8. 1 / 1
1 |
ctd
No evidence text available
27392435
Ionomycin affects USP8
1 |
Ionomycin decreases the amount of USP8. 1 / 1
1 |
ctd
No evidence text available
25613284
Hsa-miR-8066 affects USP8
1 |
Hsa-miR-8066 decreases the amount of USP8. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23313552
Hsa-miR-6768-3p affects USP8
1 |
Hsa-miR-6768-3p decreases the amount of USP8. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23313552
Hsa-miR-4753-5p affects USP8
1 |
Hsa-miR-4753-5p decreases the amount of USP8. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23313552
Hsa-miR-374a-5p affects USP8
1 |
Hsa-miR-374a-5p decreases the amount of USP8. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23622248
Hsa-miR-212-3p affects USP8
1 |
Hsa-miR-212-3p decreases the amount of USP8. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23313552
Hsa-miR-183-5p affects USP8
1 |
Hsa-miR-183-5p decreases the amount of USP8. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23622248
Hsa-miR-16-5p affects USP8
1 |
Hsa-miR-16-5p decreases the amount of USP8. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23622248
Hsa-miR-15a-3p affects USP8
1 |
Hsa-miR-15a-3p decreases the amount of USP8. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23313552
Hsa-miR-155-5p affects USP8
1 |
Hsa-miR-155-5p decreases the amount of USP8. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
22473208
Hsa-miR-132-3p affects USP8
1 |
Hsa-miR-132-3p decreases the amount of USP8. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23313552
Hsa-miR-125b-5p affects USP8
1 |
Hsa-miR-125b-5p decreases the amount of USP8. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23622248
Doxorubicin affects USP8
1 |
Doxorubicin decreases the amount of USP8. 1 / 1
1 |
ctd
No evidence text available
29803840
Dicrotophos affects USP8
1 |
Dicrotophos decreases the amount of USP8. 1 / 1
1 |
ctd
No evidence text available
28302478
Dexamethasone affects USP8
1 |
Dexamethasone decreases the amount of USP8. 1 / 1
1 |
ctd
No evidence text available
28628672
Chalcone affects USP8
| 1
Chalcone inhibits USP8. 1 / 1
| 1
reach
RA-9, a chalcone derivative with a structure similar to b-AP15, was reported to inhibit proteasomal DUBs [XREF_BIBR] as well as UCHL1, UCHL3, USP2, USP5, and USP8 [XREF_BIBR].
29039082
Calcium(2+) affects USP8
| 1
Calcium(2+) activates USP8. 1 / 1
| 1
reach
Our group found that NMDAR activation negatively regulates AMPAR ubiquitination, suggesting that the influx of calcium through NMDAR channels activates USP8.
26528125
Bisphenol F affects USP8
1 |
Bisphenol F decreases the amount of USP8. 1 / 1
1 |
ctd
No evidence text available
28628672
Benzo[a]pyrene affects USP8
1 |
Benzo[a]pyrene increases the amount of USP8. 1 / 1
1 |
ctd
No evidence text available
17879257
Bafilomycin A1 affects USP8
| 1
Bafilomycin A1 activates USP8. 1 / 1
| 1
reach
In keeping with our previous results we found an increased number of total autophagy vesicles in UBPY inactivated cells or in control cells treated with bafilomycin A1 (XREF_SUPPLEMENTARY).
26571504
ZUP1 affects USP8
| 1
ZUP1 activates USP8. 1 / 1
| 1
reach
HBX 90,397, another DUB-specific inhibitor, blocks USP8 activity.
| PMC
Vehicle Emissions affects USP8
1 |
Vehicle Emissions decreases the amount of USP8. 1 / 1
1 |
ctd
No evidence text available
28655636
reach
Ectopic expression of USP8 mutants or cleaved USP8 in murine corticotroph cell line induced higher POMC promoter activity and transcription than wild-type USP8.
26285834
USP8 affects tll1
| 1
Modified USP8 increases the amount of tll1. 1 / 1
| 1
reach
The effect was specific for USP8 because re-expression of USP8 in USP8 RNAi cells restored MFN levels (XREF_FIG).
30988163
USP8 affects proteolysis
| 1
USP8 inhibits proteolysis. 1 / 1
| 1
reach
Further studies indicated that AUF1 protein degradation was mediated by upregulating USP8 transcription, which was modulated by its negative regulatory transcription factor Sp1.
30604907
reach
Inhibition of the DUBs AMSH and UBPY inhibit the early-to-late endosomal sorting of protease activated receptor 2 (PAR2) [XREF_BIBR].
30353650
USP8 affects prostaglandin E2
| 1
USP8 inhibits prostaglandin E2. 1 / 1
| 1
reach
Moreover, USP8 downregulated several pro inflammatory cytokines [nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha), prostaglandin E 2 (PGE 2), and interleukin-1beta (IL-1beta)] in the serum and brain, and the relevant protein factors [inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2)] in the brain.
32335193
USP8 affects p14_3_3
| 1
USP8 inhibits p14_3_3. 1 / 1
| 1
reach
Recurrent gain-of-function mutations in USP8 cluster at the 14-3-3 binding site and impair the binding of 14-3-3 proteins.
29600293
USP8 affects nitric oxide
| 1
USP8 inhibits nitric oxide. 1 / 1
| 1
reach
Moreover, USP8 downregulated several pro inflammatory cytokines [nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha), prostaglandin E 2 (PGE 2), and interleukin-1beta (IL-1beta)] in the serum and brain, and the relevant protein factors [inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2)] in the brain.
32335193
USP8 affects luteolin
| 1
USP8 activates luteolin. 1 / 1
| 1
reach
We also found that USP8 siRNA blocked luteolin inhibition of pro inflammatory gene expression such as iNOS, NO, COX-2, and PGE2.
24861766
USP8 increases the amount of growth factor receptors. 1 / 1
| 1
reach
Targeting USP8 can reduce the expression of growth factor receptors that participate in cSCC development.
31705877
USP8 affects furosemide
| 1
USP8 activates furosemide. 1 / 1
| 1
reach
These binding reactions provide a scenario in which UBPY could aid transit of EGFR to ESCRT-III by helping to displace STAM2 from HD-PTP.
23477725
USP8 inhibits extrinsic apoptotic signaling pathway. 1 / 1
| 1
trips
Taken together, our data indicate that USP8 functions as a novel deubiquitylase of FLIPL and inhibits extrinsic apoptosis by stabilizing FLIPL.
27321185
USP8 inhibits extrinsic apoptotic signaling pathway via death domain receptors. 1 / 1
| 1
trips
USP8 suppresses death receptor-mediated apoptosis by enhancing FLIPL stability.
27321185
USP8 affects ethylenediamine
| 1
USP8 decreases the amount of ethylenediamine. 1 / 1
| 1
reach
Moreover, inactivation of USP8 by either USP8RNAi or USP8C> S in Drosophila embryo down-regulated En expression (XREF_FIG, compare to wild-type En staining in H) and caused lethality of the embryo or pupa (unpublished data).
22253573
USP8 affects endocytosis
| 1
USP8 inhibits endocytosis. 1 / 1
| 1
reach
The stimulation of Hh promotes Smo deubiquitination by ubiquitin specific protease 8 (USP8), which blocks Smo endocytosis and enhances Smo cell surface accumulation XREF_BIBR XREF_BIBR.
28195188
USP8 affects dendritic spine
| 1
eidos
While the enzymes mediating SHANK ubiquitination are not known , it has been recently found that USP8 selectively deubiquitinates SHANK1 and SHANK3 and modulates dendritic spine density and morphology ( Campbell and Sheng , 2018 ) .
32719102
USP8 affects cadmium(2+)
| 1
USP8 activates cadmium(2+). 1 / 1
| 1
reach
In this study, we therefore tried to address the question whether human and canine CD are caused by the same hotspot mutations in the USP8 gene.
28005997
USP8 affects Vif
| 1
USP8 inhibits Vif. 1 / 1
| 1
reach
Ectopic expression of USP8 inhibited Vif-induced A3G degradation and suppressed wild-type HIV-1 infectivity even in the presence of Vif.
34630422
USP8 affects USP8
| 1
USP8 increases the amount of USP8. 1 / 1
| 1
reach
PTEN deficient cells, which have low levels of USP8 and high levels of FLIP S, were relatively TRAIL resistant, and as previously noted, introduction of WT USP8 (but not blank vector or catalytically inactive USP8) increased USP8 levels and significantly increased the extent of TRAIL induced apoptosis (XREF_FIG).
20484045
USP8 affects Trp-Gly
| 1
USP8 activates Trp-Gly. 1 / 1
| 1
reach
Knockdown of ubpy caused trafficking defects of Wg (XREF_FIG), mimicking the mop-knockdown phenotype.
26224310
USP8 affects TP53
| 1
USP8 decreases the amount of TP53. 1 / 1
| 1
reach
Importantly, knockdown of USP8 inhibited activation of the Akt signaling pathway by decreasing the phosphorylation level of Akt and up-regulated p53 expression, while USP8 overexpression increased activation of the Akt signaling pathway in Hucct-1 cells.
32273758
USP8 affects TNF
| 1
USP8 inhibits TNF. 1 / 1
| 1
reach
Moreover, USP8 downregulated several pro inflammatory cytokines [nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha), prostaglandin E 2 (PGE 2), and interleukin-1beta (IL-1beta)] in the serum and brain, and the relevant protein factors [inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2)] in the brain.
32335193
USP8 affects TLR4
| 1
USP8 decreases the amount of TLR4. 1 / 1
| 1
reach
Mechanistically, we found that USP8 increased the expression of neuregulin receptor degradation protein-1 (Nrdp1), potently downregulated the expression of TLR4 and myeloid differentiation primary response protein 88 (MyD88) protein, and inhibited the phosphorylation of IkappaB kinase (IKK) beta and kappa B-alpha (IkappaBalpha), thereby reducing nuclear translocation of p65 by inhibiting the activation of the nuclear factor-kappaB (NF-kappaB) signaling pathway in LPS induced mice.
32335193
USP8 affects Survival
| 1
USP8 activates Survival. 1 / 1
| 1
eidos
In contrast , USP8 knockdown suppressed melanoma cell growth , survival and migration , and augmented the inhibitory effects of therapeutic drugs .
34079371
USP8 affects STAT3
| 1
Mutated USP8 decreases the amount of STAT3. 1 / 1
| 1
reach
Additionally, mutant USP8, which is unable to bind to SFN, reduces the expression of RTKs and p-STAT3.
29880877
USP8 affects STAM
| 1
USP8 inhibits STAM. 1 / 1
| 1
reach
USP8 depletion causes almost complete STAM degradation and hinders further trafficking of cargo proteins 14.
26459808
USP8 affects SNCA
| 1
USP8 activates SNCA. 1 / 1
| 1
reach
Recent data suggest that USP8 may negatively regulate degradation of alpha-synuclein by removal of Lys63 ubiquitin chains.
28064438
USP8 affects SHANK3
| 1
USP8 increases the amount of SHANK3. 1 / 1
| 1
reach
In primary rat neurons, USP8 enhances SHANK3 and SHANK1 protein levels via deubiquitination and increases dendritic spine density.
29735556
USP8 affects SHANK1
| 1
USP8 increases the amount of SHANK1. 1 / 1
| 1
reach
In primary rat neurons, USP8 enhances SHANK3 and SHANK1 protein levels via deubiquitination and increases dendritic spine density.
29735556
USP8 affects RTK
| 1
Mutated USP8 decreases the amount of RTK. 1 / 1
| 1
reach
Additionally, mutant USP8, which is unable to bind to SFN, reduces the expression of RTKs and p-STAT3.
29880877
USP8 affects RNF128
| 1
USP8 activates RNF128. 1 / 1
| 1
reach
Since Otub1was previously shown to interact with USP8, we asked whether it had any effect on USP8 modulation of GRAIL stability.
21078124
USP8 affects PIK3CA
| 1
USP8 inhibits mutated PIK3CA. 1 / 1
| 1
reach
Consistently, knockdown of USP8 significantly increased apoptosis of PIK3CA mutant cells even in the presence of glutamine (XREF_SUPPLEMENTARY).
27321283
USP8 affects PAs
| 1
Mutated USP8 activates PAs. 1 / 1
| 1
reach
Taken together, these results indicate that USP8 mutations contribute to the pathogenesis of ACTH secreting PAs.
25675982
USP8 affects Notch
| 1
USP8 activates Notch. 1 / 1
| 1
reach
The inhibition of USP8 downregulated the Notch signalling pathway via NICD destabilization, resulting in the retardation of cellular growth, wound closure, and colony forming ability of breast cancer cell lines.
31527799
USP8 affects NTRK2
| 1
USP8 activates NTRK2. 1 / 1
| 1
reach
Here, we provide mechanistic evidence indicating that ubiquitin carboxyl-terminal hydrolase 8 (USP8) modulates BDNF and TrkB dependent neuronal differentiation.
33288548
USP8 affects NTRK1
| 1
USP8 inhibits NTRK1. 1 / 1
| 1
reach
Finally we have studied the role played by USP8 on TrkA turnover; using specific siRNA for USP8 we found that USP8 knockdown increases TrkA half-life, suggesting that the deubiquitinating activity of USP8 promotes TrkA degradation.
25662281
USP8 affects MAP1LC3
| 1
USP8 inhibits MAP1LC3. 1 / 1
| 1
reach
Importantly, USP8 knock down did not impair LC3 conversion upon mTOR inhibition (XREF_SUPPLEMENTARY), further indicating that our observed effects on NCOA4 and ferritin protein levels do not reflect a general block in autophagic capacity.
28877469
USP8 affects LDLR
| 1
USP8 inhibits LDLR. 1 / 1
| 1
reach
A role has previously been described for USP8, in which its DUB activity directly decreases membrane LDLR downstream of IDOL by sorting it for lysosomal degradation 16.
26846634
USP8 affects LATS2
| 1
USP8 activates LATS2. 1 / 1
| 1
reach
Lysates from cells overexpressing HA-Lats2 were treated with the broad-specificity de-ubiquitylase USP8 or vehicle control and incubated with GST-YAP.
25026211
USP8 affects ITCH
| 1
USP8 activates ITCH. 1 / 1
| 1
reach
ITCH and AIP4 activity was activated by the deubiquitinases USP8 and USP9X, as demonstrated by RNA interference.
27203743
USP8 affects INSR
| 1
USP8 increases the amount of phosphorylated INSR. 1 / 1
| 1
reach
Interestingly, while USP8 inhibition and knockdown reduced levels of the phosphorylated insulin receptor, it had no effect on total levels of the protein (XREF_SUPPLEMENTARY).
23748694
USP8 affects IL1B
| 1
USP8 inhibits IL1B. 1 / 1
| 1
reach
Moreover, USP8 downregulated several pro inflammatory cytokines [nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha), prostaglandin E 2 (PGE 2), and interleukin-1beta (IL-1beta)] in the serum and brain, and the relevant protein factors [inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2)] in the brain.
32335193
USP8 affects IL10
| 1
USP8 activates IL10. 1 / 1
| 1
reach
Furthermore, USP8 upregulated the anti-inflammatory mediators interleukin (IL) -4 and IL-10 in the serum and brain, and promoted a shift from pro inflammatory to anti-inflammatory microglial phenotypes.
32335193
USP8 affects IFI27
| 1
Mutated USP8 increases the amount of IFI27. 1 / 1
| 1
reach
Although it was reasonable that USP8 mutations could contribute to cell cycle dysregulation and P27 underexpression in corticotroph adenomas, our data did not confirm this hypothesis.
32053843
USP8 affects HNRNPD
| 1
USP8 inhibits HNRNPD. 1 / 1
| 1
reach
Further studies indicated that AUF1 protein degradation was mediated by upregulating USP8 transcription, which was modulated by its negative regulatory transcription factor Sp1.
30604907
USP8 affects FZD
| 1
USP8 activates FZD. 1 / 1
| 1
reach
Gain and loss-of-function studies showed that USP6 stabilises the membrane pool of Fzd5 and USP8 promotes the recycling of Fzd receptors to the PM, increasing their cell surface localisation and therefore enhancing Wnt signalling both in mammalian cells and Drosophila wing.
| PMC
USP8 affects F2RL1
| 1
USP8 inhibits F2RL1. 1 / 1
| 1
reach
24 Deubiquitination may be necessary to efficiently target PAR2 to lysosomes because USP8 or AMSH knockdown moderately attenuated PAR2 degradation.
26055053
USP8 affects EEA1
| 1
USP8 activates EEA1. 1 / 1
| 1
reach
VEGFR2 also accumulated in EEA1 positive early endosomes when cells were treated with individual USP8 siRNAs to limit off-target effects.
26459808
USP8 affects DNA Damage
| 1
Modified USP8 activates DNA Damage. 1 / 1
| 1
reach
Loss of BRUCE or USP8 impairs BRIT1 deubiquitination, BRIT1 binding with gamma-H2AX, the formation of BRIT1 DNA damage foci, and chromatin relaxation.
25733871
USP8 affects Cysts
| 1
USP8 activates Cysts. 1 / 1
| 1
reach
In zebrafish, knockout (KO) of kctd17 impairs ciliogenesis in Kupffer’s vesicle and induces situs inversus [74], whereas KO of usp8 increases ciliogenesis in the pronephric duct and causes renal cysts [50].
| PMC
USP8 affects Cyclin
| 1
USP8 increases the amount of Cyclin. 1 / 1
| 1
reach
The results of western blot indicated that knockdown of USP8 down-regulated the expression of Cyclin D1, CDK4, CDK6, p-AKT, and Bcl2, and up-regulated the expression of Bax.
33293867
USP8 affects Collagen
| 1
USP8 inhibits Collagen. 1 / 1
| 1
reach
By contrast, USP8 knockdown caused the accumulation of COPII coat proteins around the cis-Golgi, promoted the intracellular trafficking of procollagen IV from the endoplasmic reticulum to the Golgi, and increased collagen IV secretion.
29604273
USP8 affects Caspase
| 1
USP8 inhibits Caspase. 1 / 1
| 1
reach
Moreover, silencing of USP8 also promoted apoptosis in cholangiocarcinoma cells by regulating the Bcl-2 and Bax axis and Caspase cascade; up-regulation of USP8 decreased apoptosis in Hucct-1 cells.
32273758
USP8 affects CYCS
| 1
USP8 decreases the amount of CYCS. 1 / 1
| 1
reach
CLOCK deubiquitylation by USP8 inhibits CLK and CYC transcription in Drosophila.
23154984
USP8 affects CXCR4
| 1
USP8 inhibits CXCR4. 1 / 1
| 1
reach
By the same mechanism, USP8 also directs the trafficking and lysosomal degradation of CXCR4 [XREF_BIBR], MET and epidermal growth factor receptor [XREF_BIBR, XREF_BIBR], implying that its loss consequent to increased RNF41 abundance would prolong and potentially amplify invasion signaling by these receptors.
26231668
USP8 affects CTNNB1
| 1
USP8 activates CTNNB1. 1 / 1
| 1
reach
USP8 and UBPY is reported to activate the Wnt and beta-catenin pathway by targeting Frizzled G protein coupled protein XREF_BIBR.
26883469
USP8 affects CHMP1B
| 1
USP8-S680A inhibits CHMP1B. 1 / 1
| 1
reach
In contrast, the expression of the wild-type or the constitutively active form USP8 S680A, but not of the catalytic mutant USP8 C748A, caused a strong reduction of the Ub-CHMP1B pool (XREF_FIG).
29933386
USP8 affects CFLAR
| 1
Modified USP8 decreases the amount of CFLAR. 1 / 1
| 1
reach
Overexpression of USP8 increased c-FLIP S ubiquitination, decreased c-FLIP S half-life, decreased c-FLIP S steady-state levels, and decreased TRAIL resistance.
23070002
USP8 affects CD63
| 1
USP8 activates CD63. 1 / 1
| 1
reach
In addition, the enlarged VEGFR2 positive endosomes did not co-distribute with late endosome marker, CD63, in cells treated with individual USP8 siRNAs.
26459808
USP8 affects BIRC6
| 1
USP8 inhibits BIRC6. 1 / 1
| 1
reach
Dex also elevated the deubiquitinating enzyme, Usp8 and Ubpy, which via Nrdp1 decreases BRUCE.
19527720
USP8 affects BCL2
| 1
USP8 inhibits BCL2. 1 / 1
| 1
reach
Moreover, silencing of USP8 also promoted apoptosis in cholangiocarcinoma cells by regulating the Bcl-2 and Bax axis and Caspase cascade; up-regulation of USP8 decreased apoptosis in Hucct-1 cells.
32273758
USP8 affects ARL6IP4
| 1
USP8 activates ARL6IP4. 1 / 1
| 1
reach
ITCH and AIP4 activity was activated by the deubiquitinases USP8 and USP9X, as demonstrated by RNA interference.
27203743
USP8 affects APP
| 1
USP8 inhibits APP. 1 / 1
| 1
reach
The endosome related deubiquitinating enzyme ubiquitin specific peptidase 8 (USP8) may inhibit the degradation of MVBs by regulating APP intracellular domain (AICD) protein levels [XREF_BIBR].
| PMC
USP7 affects USP8
| 1
USP7 inhibits USP8. 1 / 1
| 1
reach
51) specific for USP7, HBX 90,397 inhibits USP8 (3) (Ref.
22088887
USP2 affects USP8
| 1
USP2 inhibits USP8. 1 / 1
| 1
reach
Overexpression of USP2 was also shown to reduce p53 stability [XREF_BIBR], and another de-ubiquitylase USP8 (also called UBPY) promotes epithelial growth factor receptor degradation [XREF_BIBR, XREF_BIBR, XREF_BIBR].
25366495
TMEM79 affects USP8
| 1
TMEM79 inhibits USP8. 1 / 1
| 1
sparser
Given the binary protein interactions we observed among FZD, TMEM79, and USP8, we further examined how their complex assembly might occur and lead to inhibition of USP8 by TMEM79.
32924931
Sesame Oil affects USP8
1 |
Sesame Oil increases the amount of USP8. 1 / 1
1 |
ctd
No evidence text available
29191790
STAM2 affects USP8
| 1
STAM2 activates USP8. 1 / 1
| 1
reach
Reduced MET, EGFR, and STAM2 expression was consistent with attenuation of USP8 at DUBs-IN-3 concentrations that selectively increased death in cSCC cells (XREF_FIG d).
31705877
STAM affects USP8
| 1
STAM activates USP8. 1 / 1
| 1
reach
We also show that in common with AMSH, UBPY deubiquitinating enzyme activity can be stimulated by STAM but is unresponsive to its cognate CHMPs.
17711858
SP1 affects USP8
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SP1 inhibits USP8. 1 / 1
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reach
Further studies indicated that AUF1 protein degradation was mediated by upregulating USP8 transcription, which was modulated by its negative regulatory transcription factor Sp1.
30604907
SMO affects USP8
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SMO inhibits USP8. 1 / 1
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In contrast, USP8C> S increased Smo ubiquitination, which was similar to the phenotype induced by the RNAi mediated knockdown of USP8 (XREF_FIG, lanes 2 and 4, compare to lane 1, top panel).
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SMCP affects USP8
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SMCP decreases the amount of USP8. 1 / 1
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In Ts mice, MCS decreased expression of Becn1, Ccnf, Hspa1a, Usp8, and Rab27a (XREF_FIG), and in 2N mice of Rab11b (XREF_FIG).
31120189
SF1 affects USP8
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SF1 decreases the amount of USP8. 1 / 1
1 |
biopax:msigdb
No evidence text available
RORA affects USP8
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RORA decreases the amount of USP8. 1 / 1
1 |
biopax:msigdb
No evidence text available
RNF128 affects USP8
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RNF128 increases the amount of ubiquitinated USP8. 1 / 1
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reach
Furthermore, the presence of wild-type GRAIL along with USP8 increased the amount of ubiquitinated USP8, which was further enhanced when the DUB activity of USP8 was abolished.
21078124
Plant Extracts affects USP8
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Plant Extracts increases the amount of USP8. 1 / 1
1 |
ctd
No evidence text available
23557933
Particulate Matter affects USP8
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Particulate Matter decreases the amount of USP8. 1 / 1
1 |
ctd
No evidence text available
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PTPN23 affects USP8
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PTPN23 inhibits USP8. 1 / 1
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Indeed, depleting HD-PTP prevented endogenous UBPY from associating with EGFR, consistent with increased EGFR ubiquitination.
23477725
PSMD14 affects USP8
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PSMD14 activates USP8. 1 / 1
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Therefore, a second process involving DUBs is the recycling of ubiquitin by preventing its degradation, which is mediated by proteasome associated DUBs USP14, UCH-L5 and UCH37, and POH1, or receptor mediated endocytosis and lysosomal degradation associated DUBs USP8 and AMSH.
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PRKCA affects USP8
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PRKCA increases the amount of USP8. 1 / 1
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Depletion of protein kinase Calpha (PKCalpha), a target of diacylglycerol, rescued the levels of USP8 and normalized EGFR degradation in DGKdelta deficient cells.
20064931
PDGFR affects USP8
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PDGFR activates USP8. 1 / 1
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sparser
In RPE1 cells, EGFR knockdown is sufficient to repress the USP8-trichoplein-Aurora A axis and induce ciliogenesis, however, we do not exclude the involvement of other RTKs in other cell types since USP8 is also activated by PDGFRs and FGFR1-mediated phosphorylation in vitro (Supplementary Fig.  xref ).
29472535
PAX3 affects USP8
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PAX3 decreases the amount of USP8. 1 / 1
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biopax:msigdb
No evidence text available
Ossification of Posterior Longitudinal Ligament activates USP8. 1 / 1
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eidos
Then , we checked the expression of USP8 in ligament tissues from controls and patients with OPLL , and found that OPLL significantly increased the expression of USP8 ( Figure 5E ) .
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Ogd affects USP8
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Ogd activates USP8. 1 / 1
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Moreover, Nrdp1 overexpression augments OGD induced USP8 downregulation, while knockdown of Nrdp1 ameliorates this effect.
28979191
NRG1 affects USP8
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NRG1 activates USP8. 1 / 1
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Stimulation of cells with the ERBB3 ligand neuregulin-1 increases Usp8 levels, which in turn stabilizes Nrdp1.
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NGF affects USP8
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NGF activates USP8. 1 / 1
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sparser
In support of this view, NGF-activated TrkA and USP8 were shown to interact on early endosomes in PC12 cells ( xref ), and activity-dependent ubiquitylation of p75 NTR was also previously reported ( xref ).
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LRIG1 affects USP8
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LRIG1 activates USP8. 1 / 1
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In summary, the findings in the current study highlight LRIG1 mediated Met degradation and the implication of USP8 in the regulation of LRIG1 ubiquitination by a Met targeting antibody.
24828152
K 7174 affects USP8
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K 7174 increases the amount of USP8. 1 / 1
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ctd
No evidence text available
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IL2R affects USP8
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IL2R leads to the deubiquitination of ubiquitinated USP8. 1 / 1
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In particular, IL-2R signaling leads to Akt and mTOR activation, Otub1 translation, de-ubiquitination of ubiquitinated USP8, and subsequent degradation of GRAIL that permits T cell proliferation.
21078124
IGF1 affects USP8
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IGF1 inhibits USP8. 1 / 1
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reach
Further, IGF-1 could reverse the inhibitory effects of USP8 knockdown on the Akt signaling pathway and the proliferation of QBC939 and RBE cells.
32273758
HGS affects USP8
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HGS activates USP8. 1 / 1
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Overexpression of Hrs or a dominant negative mutant of SKD1, proteins that play roles in the endosomal sorting of ubiquitinated receptors, caused the accumulation of endogenous UBPY on exaggerated endosomes.
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HBX affects USP8
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HBX inhibits USP8. 1 / 1
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eidos
HBX 90,397 , another DUB-specific inhibitor , blocks USP8 activity .
| PMC
GW 7647 affects USP8
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GW 7647 inhibits USP8. 1 / 1
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Moreover, GW7647 did not inhibit USP5 and USP8.
22118673
ESRRA affects USP8
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ESRRA decreases the amount of USP8. 1 / 1
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biopax:msigdb
No evidence text available
ERBB2 affects USP8
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ERBB2 activates USP8. 1 / 1
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reach
Alternatively, the stoichiometry of ErbB2 induced Usp8 tyrosine phosphorylation may be lower than in the case of EGFR.
21044682
E4F1 affects USP8
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E4F1 decreases the amount of USP8. 1 / 1
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biopax:msigdb
No evidence text available
Dietary Fats affects USP8
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Dietary Fats increases the amount of USP8. 1 / 1
1 |
ctd
No evidence text available
25016146
CHMP4B affects USP8
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CHMP4B activates USP8. 1 / 1
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reach
Altogether, these data indicate that CHMP4B binds the MIT domain of UBPY and the HD-PTP Bro1 domain simultaneously, though it is formally possible that CHMP4B additionally activates UBPY MIT to bind H[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
23477725
CBL affects USP8
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CBL inhibits USP8. 1 / 1
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reach
We propose that Cbl inhibits the function of Ubpy.
26224310
BIRC6 affects USP8
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BIRC6 deubiquitinates USP8. 1 / 1
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In fact, the BRUCE associated deubiquitylating enzyme UBPY harbors a so called MIT-domain that mediates association with proteins of the ESCRTIII complex (Row et al., 2007).
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Aroclor 1254 affects USP8
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Aroclor 1254 decreases the amount of USP8. 1 / 1
1 |
ctd
No evidence text available
23650126
3-isobutyl-1-methyl-7H-xanthine decreases the amount of USP8. 1 / 1
1 |
ctd
No evidence text available
28628672
2-hydroxypropanoic acid decreases the amount of USP8. 1 / 1
1 |
ctd
No evidence text available
30851411
2,4,6-trinitrobenzenesulfonic acid decreases the amount of USP8. 1 / 1
1 |
ctd
No evidence text available
23537331