USP20 Data Analysis

HGNC Gene Name
ubiquitin specific peptidase 20
HGNC Gene Symbol
USP20
Identifiers
hgnc:12619 NCBIGene:10868 uniprot:Q9Y2K6
Orthologs
mgi:1921520 rgd:1305621
INDRA Statements
deubiquitinations all statements
Pathway Commons
Search for USP20
Number of Papers
48 retrieved on 2022-05-22

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

Dependency GO Term Enrichment

Gene set enrichment analysis was done on the genes correlated with USP20using 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

Transcriptomics

The following table shows the significantly differentially expressed genes after knocking out USP20 using CRISPR-Cas9.

Knockout Differential Expression

Symbol Name log2-fold-change p-value p-value (adj.)
RPL13 ribosomal protein L13 6.13e-01 2.33e-11 1.75e-07
RPS15 ribosomal protein S15 9.60e-01 7.09e-09 2.67e-05
NSA2 NSA2 ribosome biogenesis factor 8.34e-01 1.44e-07 3.60e-04
RPS10-NUDT3 RPS10-NUDT3 readthrough -6.94e-01 1.39e-06 2.62e-03
RBM3 RNA binding motif protein 3 4.70e-01 2.31e-06 3.48e-03
S100A6 S100 calcium binding protein A6 3.93e-01 5.98e-06 7.49e-03
CALM2 calmodulin 2 2.52e-01 1.45e-05 1.56e-02
ANKRD1 ankyrin repeat domain 1 -3.67e-01 3.12e-05 2.93e-02
MTCO2P12 MT-CO2 pseudogene 12 -3.52e-01 5.99e-05 4.70e-02
NUDT4 nudix hydrolase 4 -4.12e-01 6.25e-05 4.70e-02
C4BPB complement component 4 binding protein beta 6.98e-01 9.47e-05 4.92e-02
CTNNBL1 catenin beta like 1 5.40e-01 8.35e-05 4.92e-02
MORF4L2 mortality factor 4 like 2 3.53e-01 9.82e-05 4.92e-02
TOMM6 translocase of outer mitochondrial membrane 6 -4.87e-01 9.41e-05 4.92e-02

Gene Set Enrichment Analysis

There were too few differentially expressed genes to run a meaningful GSEA.

Literature Mining

INDRA was used to automatically assemble known mechanisms related to USP20 from literature and knowledge bases. The first section shows only DUB activity and the second shows all other results.

Deubiquitinase Activity

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USP20 deubiquitinates CLSPN. 10 / 11
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CLASPIN was also deubiquitinated by bacterially produced GST-USP20, but not by the catalytically inactive mutant GST USP20 (C154S), in the in vitro deubiquitination assays.

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These results revealed that USP20 mediated Claspin downregulation did not occur at the gene transcription level, just as the prior study reported that USP20 deubiquitinate and stabilize Claspin.

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USP20 in turn deubiquitinates and stabilizes Claspin and enhances the activation of ATR-Chk1 signaling.

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Next, we tested whether USP20 deubiquitinates Claspin.

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These results suggest that USP20 deubiquitinates Claspin in cells.

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USP20 deubiquitinates and stabilizes Claspin.

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USP20 deubiquitinates and stabilizes Claspin, which in turn facilitate the activation of cell-cycle checkpoint following DNA damage.

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Unbound USP20 is enzymatically active and mediates Claspin deubiquitination and stabilization, this way promoting Chk1 activation [49,50].

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USP20 in turn deubiquitinates and stabilizes Claspin and enhances the activation of ATR-Chk1 signaling.

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To determine whether USP20 directly deubiquitinates Claspin, we performed an in vitro deubiquitination assay.
USP20 deubiquitinates TRAF6. 9 / 9
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For example, Junichiro et al. demonstrated that USP21 constitutively deubiquitinates RIP1 in vitro and in vivo [40]; and a previous study has reported that USP20 deubiquitinates TRAF6 and Tax in vivo [40].

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Here, we report that ubiquitin specific peptidase USP20 deubiquitinates TRAF6 and Tax and suppresses interleukin 1beta (IL-1beta) - and Tax induced NF-kappaB activation.

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54 Ubiquitinated beta-arrestin2 promotes NF-kappaB signaling in SMCs, whereas deubiquitinated beta-arrestin2 attenuates NF-kappaB signaling by scaffolding the deubiquitinase USP20, that in turn deubiquitinates TRAF6, which blocks the NF-kappaB signaling cascade.

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For example, USP11 negatively regulates TNFα-induced NF-κB activation associated with IκBα and attenuates IκBα degradation [34]; USP20 deubiquitinates TRAF6 and suppresses interleukin 1β (IL-1β)- and Tax-induced NF-κB activation [40]; Katrin et al. showed that USP15 regulates IκBα/NF-κB by deubiquitinylation IκBα[44]; and USP31 inhibits TNFα, CD40, TRAF2, TRAF6 and IKKβ-mediated NF-κB activation [45].

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TRAF6 activity can be impeded by deubiquitinating enzymes like ubiquitin specific protease 20 (USP20), which can reverse TRAF6 autoubiquitination, and by association with the multifunctional adaptor protein beta-arrestin2.

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With purified proteins and in intact cells, our protein interaction studies showed that TRAF6/USP20 association and subsequent USP20-mediated TRAF6 deubiquitination were β-arrestin2-dependent.

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For example, USP11 negatively regulates TNFalpha induced NF-kappaB activation associated with IkappaBalpha and attenuates IkappaBalpha degradation [XREF_BIBR]; USP20 deubiquitinates TRAF6 and suppresses interleukin 1beta (IL-1beta) - and Tax induced NF-kappaB activation [XREF_BIBR]; Katrin et al. showed that USP15 regulates IkappaBalpha and NF-kappaB by deubiquitinylation IkappaBalpha [XREF_BIBR]; and USP31 inhibits TNFalpha, CD40, TRAF2, TRAF6 and IKKbeta mediated NF-kappaB activation [XREF_BIBR].

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For example, Junichiro et al. demonstrated that USP21 constitutively deubiquitinates RIP1 in vitro and in vivo [XREF_BIBR]; and a previous study has reported that USP20 deubiquitinates TRAF6 and Tax in vivo [XREF_BIBR].

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We report that two ubiquitin specific peptidases, USP20 and USP33, deubiquitinate TRAF6 and suppress IL-1beta-induced NF-kappaB activation.
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USP20 deubiquitinates HIF1A. 5 / 5
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VDU2 can specifically deubiquitinate and stabilize HIF-1alpha and, therefore, increase expression of HIF-1alpha targeted genes, such as vascular endothelial growth factor (VEGF).

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In addition, VDU2, but not VDU1, is able to interact with and deubiquitinate HIF1alpha, and rescue it from proteasome mediated degradation.

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USP20 stabilizes HIF-1α by abolishing von Hippel-Lindau protein (pVHL)-E3 ligase complex-mediated HIF-1α degradation.

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In addition, it was shown that VDU2 but not VDU1 can deubiquitylate HIF-1alpha and increase it 's half-life.

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One of them, USP-20, deubiquitinates HIF-1alpha and therefore tends to stabilize it [46] by preventing its proteasomal degradation.
USP20 deubiquitinates Tax. 5 / 5
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Here, we report that ubiquitin specific peptidase USP20 deubiquitinates TRAF6 and Tax and suppresses interleukin 1beta (IL-1beta) - and Tax induced NF-kappaB activation.

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We find that USP20 deubiquitinates Tax and inhibits Tax induced NF-kappaB activation, consistent with Tax being a substrate of USP20.
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For example, Junichiro et al. demonstrated that USP21 constitutively deubiquitinates RIP1 in vitro and in vivo [XREF_BIBR]; and a previous study has reported that USP20 deubiquitinates TRAF6 and Tax in vivo [XREF_BIBR].

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In further support of this, the deubiquitinating enzyme (DUB) USP20 deubiquitinates Tax to negatively regulate activation of IKK [XREF_BIBR].

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For example, Junichiro et al. demonstrated that USP21 constitutively deubiquitinates RIP1 in vitro and in vivo [40]; and a previous study has reported that USP20 deubiquitinates TRAF6 and Tax in vivo [40].
USP20 deubiquitinates RIPK1. 3 / 3
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RIPK1 was deubiquitinated by purified USP20 in vitro.

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TNF evoked = ~ 2-fold more RIPK1 ubiquitination in SMC-DN-USP20-transgenic than in control SMCs, and RIPK1 was deubiquitinated by purified USP20 in vitro.

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Conclusions- USP20 attenuates TNF- and IL-1β-evoked atherogenic signaling in SMCs, by deubiquitinating RIPK1, among other signaling intermediates.
USP20 deubiquitinates ULK1. 2 / 2
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USP20 interacts with and deubiquitinates ULK1, thus protecting it from degradation.

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The deubiquitination of ULK1 by USP20 allows for its stabilization and promotion of autophagy induction.
USP20 deubiquitinates MAPK6. 2 / 2
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In this study, we carried out an unbiased functional loss-of-function screen of the human deubiquitinating enzyme (DUB) family and identified ubiquitin-specific protease 20 (USP20) as a novel ERK3 regulator.| USP20 interacts with and deubiquitinates ERK3 both in vitro and in intact cells.

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USP20 interacts with and deubiquitinates ERK3 both in vitro and in intact cells.
USP20 deubiquitinates ARRB2. 2 / 2
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54 Ubiquitinated beta-arrestin2 promotes NF-kappaB signaling in SMCs, whereas deubiquitinated beta-arrestin2 attenuates NF-kappaB signaling by scaffolding the deubiquitinase USP20, that in turn deubiquitinates TRAF6, which blocks the NF-kappaB signaling cascade.

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Importantly, a double knockdown of USP20 and USP33 enhances the extent of beta-arrestin-2 ubiquitination and increases beta 2 AR degradation.
USP20 leads to the deubiquitination of AR. 1 / 1
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104 Two DUBs USP20 and USP33 have been shown to mediate deubiquitination of beta 2 AR.
USP20 deubiquitinates RAD17. 1 / 1
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Similar to Chk1 and Rad17, which enhance recombinational repair of collapsed replication forks, we demonstrate that USP20 depletion impairs DNA double strand break repair by homologous recombination.
USP20 leads to the deubiquitination of CTNNB1. 1 / 1
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Moreover, knockdown of USP20 increases beta-catenin polyubiquitination, which enhances beta-catenin turnover and cell sensitivity to chemotherapy.
USP20 deubiquitinates ADRB2. 1 / 1
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USP20-C154S deubiquitinates CLSPN. 1 / 1
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CLASPIN was also deubiquitinated by bacterially produced GST-USP20, but not by the catalytically inactive mutant GST USP20 (C154S), in the in vitro deubiquitination assays.

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USP20 also deubiquitinates hypoxia inducible factor-1 alpha (HIF-1alpha), promoting HIF-1alpha stability and consequently the expression of its target genes.
USP20 deubiquitinates DIO2. 1 / 1
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Ubiquitinated D2 can be either targeted to proteasomal degradation or reactivated by deubiquitination, a process that is mediated by the deubiquitinases USP20/33 and is important in adaptive thermogenesis.
USP20 deubiquitinates PKM. 1 / 1
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From this evidence, it is expected that USP20 would be associated with the metabolic pathway through the regulation of PKM2 ubiquitination.
USP20 deubiquitinates ubiquitinated VHL. 1 / 1
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Can VDU1 or VDU2 deubiquitinate the ubiquitinated pVHL to salvage it from degradation on certain conditions?
USP20 deubiquitinates ubiquitinated CLSPN. 1 / 1
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USP20 in turn deubiquitinates K48-linked-polyubiquitinated CLASPIN, stabilizing CLASPIN and ultimately promoting CHK1 phosphorylation and CHK1 directed checkpoint activation.
USP20 deubiquitinates STING1. 1 / 1
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USP18 recruits USP20 to promote innate antiviral response through deubiquitinating STING/MITA
USP20 deubiquitinates CNTN2. 1 / 1
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The ubiquitin specific peptidase USP20 (ubiquitin specific peptidase) deubiquitinates Tax-1 and suppresses IL-1beta- and Tax-1-induced NF-kappaB activation XREF_BIBR.

Other Statements

psp cbn pc bel_lc signor biogrid lincs_drug tas hprd trrust ctd vhn pe drugbank omnipath conib crog dgi | rlimsp isi tees geneways eidos trips medscan sparser reach
USP20 affects CLSPN
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USP20 activates CLSPN.
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USP20 activates CLSPN. 3 / 9
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USP20 promotes CLASPIN stability through deubiquitination.

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Given that HERC2 is a component of the replication complex, our data shown in this report suggest that HERC2 and USP20 coordinately modulate CLASPIN stability during S-phase and in response to replication stress.

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These results revealed that USP20 mediated Claspin downregulation did not occur at the gene transcription level, just as the prior study reported that USP20 deubiquitinate and stabilize Claspin.
USP20 increases the amount of CLSPN.
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USP20 increases the amount of CLSPN. 1 / 2
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Furthermore, reconstitution of WT USP20 but not catalytically inactive mutant of USP20 (USP20CA) in USP20 depleted cells restored Claspin protein levels.
Modified USP20 increases the amount of CLSPN. 1 / 1
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As shown in XREF_FIG, overexpression of USP20 increased the protein level of Claspin without the change of mRNA level.
Mutated USP20 increases the amount of CLSPN. 1 / 1
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Furthermore, reconstitution of WT USP20 but not catalytically inactive mutant of USP20 (USP20CA) in USP20 depleted cells restored Claspin protein levels.
USP20 inhibits CLSPN.
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USP20-C154S inhibits CLSPN. 1 / 1
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Concomitantly, expression of the catalytically inactive mutant FLAG USP20 (C154S) reduced the half-life of CLASPIN.
USP20 inhibits CLSPN. 1 / 1
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Furthermore, downregulation of USP20 blocked UV induced Claspin upregulation.
USP20 decreases the amount of CLSPN.
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USP20 decreases the amount of CLSPN. 1 / 1
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Prior studies have demonstrated that USP20 regulate the cell proliferation through the ATK-Claspin-CHK signaling pathway, and downregulation of USP20, could reduce the expression of Claspin through the ubiquitin-proteasome degradation and promote the DNA synthesis, suggesting a defect in the intra-S-phase checkpoint.
USP20 affects CHEK1
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USP20 activates CHEK1.
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USP20 activates CHEK1. 4 / 8
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USP20 promotes CHK1 activation in response to replication stress or UV radiation.

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Taken together, these results indicate that USP20 promotes CHK1 activation in response to HU induced replication stress or UV irradiation.

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Upon replication stress, ATR mediated phosphorylation of USP20 promotes dissociation of HERC2 from USP20, stabilizes USP20 and its association with CLASPIN, thus increasing CALSPIN stability and ensuring CHK1 activation.

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To test if USP20 mediated stability of CLASPIN promotes CHK1 activation upon replication stress, we expressed wild-type FLAG-CLASPIN in USP20 depleted cells.
USP20 inhibits CHEK1.
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USP20 inhibits CHEK1. 1 / 1
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In a candidate screen of ubiquitin specific processing proteases (USPs) for modulating CHK1 activation, we revealed that inhibition of USP20 expression in 293T cells delayed HU induced CHK1 activation, whereas expression of siRNA resistant form of FLAG-USP20res in the endogenous USP20 depleted cells restored HU induced CHK1 activation kinetics.
USP20-C154S inhibits CHEK1. 1 / 1
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Concomitantly, expression of the catalytically inactive mutant FLAG USP20 (C154S) attenuated HU induced CHK1 activation.

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Silencing of USP20 increases proliferation in GC cells.

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In line with the clinical outcomes, we found that the overexpression of USP20 could, on one hand, suppress cell proliferation and delay G1-S cell cycle transition, and on the other hand, enhance autophagy in GC cells.

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Since overexpression of USP20 inhibits the proliferation of ATL cells, it raises the possibility that induction of USP20 could be used to inhibit HTLV induced oncogenesis.

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Experimentally, small interfering RNA mediated knockdown of USP20 expression significantly promoted cell proliferation, accelerated G1-S phase transition and attenuated the autophagy activity.

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In HTLV-1-transformed cells, the transcription of USP20 is reduced compared with HTLV-1-negative T cells, and ectopic USP20 expression was found to inhibit the proliferation of an HTLV-1-transformed cell line, MT4.
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These finding revealed that USP20 could modulate GC cell proliferation.

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Depletion of several DUBs caused either resistance or hypersensitivity to HU treatment; among them, USP20 knockdown showed most significant hypersensitivity to HU treatment, while knockdown of USP20 slightly decreased cell proliferation in untreated cells.
USP20 affects NFkappaB
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USP20 inhibits NFkappaB.
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USP18 deficiency or knockdown of USP20 resulted in enhanced K48 linked ubiquitination and accelerated degradation of STING, and impaired activation of IRF3 and NF-kappaB as well as induction of downstream genes after infection with DNA virus HSV-1 or transfection of various DNA ligands.

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Silencing USP20 in SMCs with siRNA (small interfering RNA) augmented NFkappaB activation by = ~ 50% in response to either TNF or IL-1beta (interleukin-1beta).

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XREF_BIBR USP20 inhibits NF-kappaB activation via Toll like receptor (TLR) 4, XREF_BIBR IL-1R, and the TNF XREF_BIBR inflammatory pathway in VSMCs.

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XREF_BIBR This study showed that USP18 or USP20 deficiency significantly inhibited HSV-I or cytosolic DNA activation of both NF-kappaB and IRF3, and type-I IFN and proinflammatory cytokine expression.

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USPs are the most abundant DUBs, with approximately 60 proteases in humans. xref USP20 inhibits NF-κB activation via Toll-like receptor (TLR)4, xref IL-1R, and the TNF xref inflammatory pathway in VSMCs.
USP20 activates NFkappaB.
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USP20 is downregulated in HTLV-1 infected cell lines, presumably to promote high levels of NF-kappaB activation, although the exact mechanism is unclear [XREF_BIBR].

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Coimmunoprecipitation experiments revealed that USP20 associates with several components of the TNFR1 (TNF receptor-1) signaling pathway, including RIPK1 (receptor interacting protein kinase 1), a critical checkpoint in TNF induced NFkappaB activation and inflammation.
USP20 affects HIF1A
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USP20 activates HIF1A.
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USP20 activates HIF1A. 2 / 4
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Up-regulation of Usp20, a deubiquitinase that acts on Hif1a and other proteins 24, should reduce degradation of Hif1a.

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Therefore, targeting USP20 can induce degradation of HIF-1alpha and be a potential drug target for human cancer.
USP20 increases the amount of HIF1A.
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Modified USP20 increases the amount of HIF1A. 1 / 1
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Thus, overexpression of VDU2 increases expression of HIF-1alpha targeted genes, such as VEGF.
USP20 increases the amount of HIF1A. 1 / 1
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The previous study has shown that Usp20 increases the expression of HIF1A XREF_BIBR, XREF_BIBR, which is reported as a metabolic switch for an early stage of iPSC 20.
HERC2 affects USP20
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HERC2 inhibits USP20.
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HERC2 inhibits USP20. 4 / 4
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HERC2 promotes USP20 degradation.

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Here we found that HERC2 antagonized USP20 function and negatively regulated the replication stress signaling pathway.

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In HERC2 depleted cells, USP20 and its substrates Claspin were significantly upregulated and the phosphorylation of CHK1 is more sustained, even at later time points.

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Taken together, these results suggested that HERC2 functions as an E3 ligase of USP20 and negatively regulates USP20 in unstressed cells.
HERC2 increases the amount of USP20.
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HERC2 increases the amount of USP20. 1 / 1
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As shown in Figure XREF_FIG and XREF_FIG, downregulation of HERC2 resulted in upregulation of USP20 levels and protein stability.
USP20 affects autophagy
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Our result found that silencing of USP20 could inhibit autophagy, not singly but in pairs, the overexpression of USP33, which is the homology of USP20, could deubiquitinate RALB at Lys 47, and then regulate assembly of the RALB, EXO84, and beclin1 complex that initiated autophagy.

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Thus, whether the autophagy caused by USP20 could contribute to the inhibition of tumor growth is worthy of investigation in a further study.

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Experimentally, small interfering RNA mediated knockdown of USP20 expression significantly promoted cell proliferation, accelerated G1-S phase transition and attenuated the autophagy activity.

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On the contrary, autophagy activity was enhanced by the USP20 overexpression (XREF_FIG).
USP20 affects TNF
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USP20 inhibits TNF. 4 / 4
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USP20 (Ubiquitin Specific Protease 20) Inhibits TNF (Tumor Necrosis Factor)-Triggered Smooth Muscle Cell Inflammation and Attenuates Atherosclerosis.

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Conclusions- USP20 attenuates TNF- and IL-1beta-evoked atherogenic signaling in SMCs, by deubiquitinating RIPK1, among other signaling intermediates.

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XREF_BIBR USP20 inhibits NF-kappaB activation via Toll like receptor (TLR) 4, XREF_BIBR IL-1R, and the TNF XREF_BIBR inflammatory pathway in VSMCs.

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Silencing USP20 in SMCs with siRNA (small interfering RNA) augmented NFkappaB activation by = ~ 50% in response to either TNF or IL-1beta (interleukin-1beta).
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Pirinixic acid increases the amount of USP20. 3 / 3
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USP20 (Ubiquitin Specific Protease 20) Inhibits TNF (Tumor Necrosis Factor)-Triggered Smooth Muscle Cell Inflammation and Attenuates Atherosclerosis.

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Thus, USP20 inhibits SMC inflammation in response to the atherogenic cytokine IL-1β, as it does to the atherogenic activation of TLR4. xref
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Coimmunoprecipitation experiments revealed that USP20 associates with several components of the TNFR1 (TNF receptor-1) signaling pathway, including RIPK1 (receptor interacting protein kinase 1), a critical checkpoint in TNF induced NFkappaB activation and inflammation.
USP20 affects USP20
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USP20 activates USP20.
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USP20 activates USP20. 2 / 2
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These suggest that ATR mediated phosphorylation of USP20 promotes dissociation of USP20 from HERC2, and this dissociation would stabilize CLASPIN and promote CHK1 activation.

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] Although deubiquitinating STING alone , USP20 can be recruited by USP18 , thus causing USP20 to remove K48-linked polyubiquitin chains more efficiently , even at a low dose .
USP20 inhibits USP20.
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USP20 inhibits USP20. 1 / 1
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Under unperturbed condition, HERC2 ubiquitinates USP20 and promotes ubiquitination mediated proteasomal degradation of USP20, regulating the status of K48 linked polyubiquitination of CLASPIN and ensuring appropriate protein levels of CLASPIN during the S-phase.

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USP20 links feeding induced cholesterol synthesis and energy expenditure.

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Genetic deletion or pharmacological inhibition of USP20 markedly decreases diet induced body weight gain, reduces lipid levels in the serum and liver, improves insulin sensitivity and increases energy expenditure.
USP20 affects cell cycle
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As shown in XREF_FIG, the silencing of USP20 expression accelerated the G1-S cell cycle transition which is accompanied by decrease in the percentage of G1 cells (down to 54.05%) and increase in the percentage of cells in the S phase (up to 37.62%), and the tendency was also consistent with MKN45-siUSP20 cells and BGC-823-siUSP20 cells (P < 0.05; XREF_FIG and XREF_FIG).

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In line with the clinical outcomes, we found that the overexpression of USP20 could, on one hand, suppress cell proliferation and delay G1-S cell cycle transition, and on the other hand, enhance autophagy in GC cells.
USP20 affects IRF3
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USP20 inhibits IRF3. 2 / 2
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XREF_BIBR This study showed that USP18 or USP20 deficiency significantly inhibited HSV-I or cytosolic DNA activation of both NF-kappaB and IRF3, and type-I IFN and proinflammatory cytokine expression.

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USP18 deficiency or knockdown of USP20 resulted in enhanced K48 linked ubiquitination and accelerated degradation of STING, and impaired activation of IRF3 and NF-kappaB as well as induction of downstream genes after infection with DNA virus HSV-1 or transfection of various DNA ligands.
USP20 affects IL1B
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USP20 inhibits IL1B. 2 / 2
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Silencing USP20 in SMCs with siRNA (small interfering RNA) augmented NFkappaB activation by = ~ 50% in response to either TNF or IL-1beta (interleukin-1beta).

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For example , USP11 negatively regulates TNFalpha-induced NF-kappaB activation associated with IkappaBalpha and attenuates IkappaBalpha degradation [ 34 ] ; USP20 deubiquitinates TRAF6 and suppresses interleukin 1beta ( IL-1beta ) - and Tax-induced NF-kappaB activation [ 40 ] ; Katrin et al. showed that USP15 regulates IkappaBalpha / NF-kappaB by deubiquitinylation IkappaBalpha [ 44 ] ; and USP31 inhibits TNFalpha , CD40 , TRAF2 , TRAF6 and IKKbeta-mediated NF-kappaB activation [ 45 ] .
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Silencing of USP20 increases proliferation in GC cells.
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These finding revealed that USP20 could modulate GC cell proliferation.
USP20 affects RAD17
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Modified USP20 increases the amount of RAD17. 1 / 1
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It was also noted that inhibition of USP20 expression decreased RAD17 protein levels.
USP20 increases the amount of RAD17. 1 / 1
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Consistent with this report, we found knockdown of USP20 in cells decreased Rad17 levels.
3,4-methylenedioxymethamphetamine increases the amount of USP20.
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3,4-methylenedioxymethamphetamine decreases the amount of USP20.
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Urethane affects USP20
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Urethane increases the amount of USP20. 1 / 1
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Tetrachloromethane decreases the amount of USP20. 1 / 1
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Sodium arsenite increases the amount of USP20. 1 / 1
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Silicon dioxide decreases the amount of USP20. 1 / 1
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Progesterone increases the amount of USP20. 1 / 1
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Potassium chromate increases the amount of USP20. 1 / 1
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Phenobarbital increases the amount of USP20. 1 / 1
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Methamphetamine increases the amount of USP20. 1 / 1
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Lipopolysaccharide increases the amount of USP20. 1 / 1
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Leflunomide affects USP20
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Leflunomide decreases the amount of USP20. 1 / 1
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Hydroperoxide decreases the amount of USP20. 1 / 1
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Hsa-miR-26b-5p decreases the amount of USP20. 1 / 1
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biopax:mirtarbase
No evidence text available
Genistein affects USP20
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Genistein decreases the amount of USP20. 1 / 1
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ctd
No evidence text available
Flutamide affects USP20
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Flutamide increases the amount of USP20. 1 / 1
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ctd
No evidence text available
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Carbon nanotube decreases the amount of USP20. 1 / 1
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ctd
No evidence text available
Bisphenol A affects USP20
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Bisphenol A decreases the amount of USP20. 1 / 1
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ctd
No evidence text available
Bis(2-ethylhexyl) phthalate increases the amount of USP20. 1 / 1
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ctd
No evidence text available
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Benzo[a]pyrene increases the amount of USP20. 1 / 1
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ctd
No evidence text available
All-trans-retinoic acid increases the amount of USP20. 1 / 1
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ctd
No evidence text available

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VDU1 and VDU2, a closely related isoform, have been shown to increase half-life of type 2 iodothyronine deiodinase by their deubiquitinating activity [23].
USP20 affects cholesterol
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USP20 links feeding induced cholesterol synthesis and energy expenditure.
USP20 affects cell growth
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As shown in XREF_FIG, silencing of USP20 significantly promoted cell growth in monolayer culture, and further experimental results revealed that the proliferation ability of MGC-803-USP20 cells were lower than that of MGC-803-NC cells (XREF_FIG).
USP20 affects cell death
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Because our results suggest that the USP20-p62 axis is responsible for PKCzeta-mediated NF-kappaB activation for cell survival , USP20 depletion may promote cell death .
USP20 affects behavior
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Notably , suppressing PTEN with its specific inhibitor dramatically abolished the function of USP20 to ameliorate neuroinflammation and neuron death induced by OGD / R. Collectively , our results illustrated that USP20 could effectively mitigate the severity of cerebral ischemic stroke and improve behavior deficits in MCAO-operated mice , and identified the USP20 / PTEN axis as a promising therapeutic target for ischemic stroke treatment .
USP20 affects USP33
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USP20 activates USP33. 1 / 1
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The closely related DUBs, USP20 and USP33, deubiquitylate activated beta-adrenergic receptors as well as the adaptor and signalling protein beta-arrestin (in the case of USP33), to favour recycling from endosomes, despite largely being associated with the secretory pathway 75, 76, 77.
USP20 affects TRAF6
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USP20 activates TRAF6. 1 / 1
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For example, USP17 and USP20 were found to target RIG-I and TRAF6 respectively, thereby functioning as novel regulators of antiviral innate immune responses [XREF_BIBR, XREF_BIBR].
USP20 affects STING1
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USP20 inhibits STING1. 1 / 1
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USP18 deficiency or knockdown of USP20 resulted in enhanced K48 linked ubiquitination and accelerated degradation of STING, and impaired activation of IRF3 and NF-kappaB as well as induction of downstream genes after infection with DNA virus HSV-1 or transfection of various DNA ligands.
USP20 affects SNAI2
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USP20 activates SNAI2. 1 / 1
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Deubiquitinase USP20 promotes breast cancer metastasis by stabilizing SNAI2.

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All these effects mediated by USP20 during cerebral I/R injury were confirmed in the cultured primary microglial cells and cortical neurons stimulated by oxygen-glucose deprivation and reoxygenation (OGD/R).

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Deubiquitinase USP20 promotes breast cancer metastasis by stabilizing SNAI2.
USP20 affects MAPK6
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USP20 decreases the amount of MAPK6. 1 / 1
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The overexpression of USP20 results in the stabilization and accumulation of the ERK3 protein, whereas USP20 depletion reduces the levels of ERK3.
USP20 affects Interferon
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XREF_BIBR This study showed that USP18 or USP20 deficiency significantly inhibited HSV-I or cytosolic DNA activation of both NF-kappaB and IRF3, and type-I IFN and proinflammatory cytokine expression.
USP20 affects Infections
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The complementation of STING into Usp20 (-/-) cells remarkably restores HSV-1-triggered signaling and inhibits HSV-1 infection (92).
USP20 affects INS
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USP20 activates INS. 1 / 1
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Genetic deletion or pharmacological inhibition of USP20 markedly decreases diet induced body weight gain, reduces lipid levels in the serum and liver, improves insulin sensitivity and increases energy expenditure.

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USP20 promotes genome stability and suppresses xenograft tumor growth.
USP20 affects DDX58
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USP20 activates DDX58. 1 / 1
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For example, USP17 and USP20 were found to target RIG-I and TRAF6 respectively, thereby functioning as novel regulators of antiviral innate immune responses [XREF_BIBR, XREF_BIBR].
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Furthermore, reconstitution of WT USP20 but not USP20-4 mut rescued the cell viability after UV treatment and restored UV or HU induced intra-S-phase checkpoint.
USP20 affects BCAM
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USP20 activates BCAM. 1 / 1
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Lu et al. demonstrated the post-prandial increase in insulin and the glucose concentration stimulates mTORC1 to phosphorylate the deubiquitylase ubiquitin-specific peptidase 20 (USP20) at S132 and S134, which is recruited to the HMGCR complex and antagonizes its degradation (Lu et al., 2020).
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147 In addition , USP20 attenuated atherosclerosis in an LDLr - / - mouse model by inhibiting NF-kappaB activation in vivo.148 Therefore , increased expression / activity of USP20 may offer protection against inflammatory pathways in patients with ISR .
USP20 affects Ala-Pro
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USP20 activates Ala-Pro. 1 / 1
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In contrast, the overexpression of Usp26 decreased the number of AP + colonies, while overexpression of Usp20 increased the number of AP + colonies.
USP20 affects ADRB1
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USP20 inhibits ADRB1. 1 / 1
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For example, ubiquitin carboxyl-terminal hydrolase 20 (USP20) knockout reduces beta1-adrenergic receptor (beta1AR)-induced cardiac contractility and relaxation.
RAD17 affects USP20
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RAD17 activates USP20. 1 / 1
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Nevertheless, in USP20 knockdown cells, reconstitution of Claspin was able to rescue phospho-CHK1 levels and significantly suppress tumorigenesis, even if Rad17 levels was decreased, suggesting that Claspin is an important target of USP20 in mediating checkpoint activation and tumor suppression.
PTEN affects USP20
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PTEN activates USP20. 1 / 1
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Notably, suppressing PTEN with its specific inhibitor dramatically abolished the function of USP20 to ameliorate neuroinflammation and neuron death induced by OGD/R.
PKA affects USP20
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PKA inhibits USP20. 1 / 1
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Concomitant inhibition of the deubiquitinase USP20 (Ubiquitin-specific-processing protease 20) by PKA favors ubiquitylation and degradation of the receptor by NEDD4 ( xref ; xref ).
Niclosamide affects USP20
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Niclosamide increases the amount of USP20. 1 / 1
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ctd
No evidence text available

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Our experiments showed that hVDU2 protein was extremely stable in the group without co-transfection of pVHL during cycloheximide treatment, and MG132 did not significantly increase the level of VDU2 p[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
MAPK6 affects USP20
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MAPK6 activates USP20. 1 / 1
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Mechanistically, ERK3 expression level in cancer cells was shown to be upregulated by BRAF (through increasing ERK3 mRNA) 11, BMI1 (by suppressing let-7i which targets ERK3 mRNA) 12 and USP20 (by deubiquitinating and stabilizing ERK3 protein) 13.
CLSPN affects USP20
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CLSPN activates USP20. 1 / 1
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Nevertheless, in USP20 knockdown cells, reconstitution of Claspin was able to rescue phospho-CHK1 levels and significantly suppress tumorigenesis, even if Rad17 levels was decreased, suggesting that Claspin is an important target of USP20 in mediating checkpoint activation and tumor suppression.
CHEK1 affects USP20
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CHEK1 activates USP20. 1 / 1
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We found that overexpression of FLAG-CLASPIN corrected the delay of USP20 depletion-induced CHK1 activation in response to HU treatment (Figure xref ).
AZM551248 affects USP20
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AZM551248 decreases the amount of USP20. 1 / 1
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ctd
No evidence text available
ATR affects USP20
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ATR activates USP20. 1 / 1
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Since USP20 is upregulated after replication stress, we sought to determine whether USP20 is modulated by ATR in response to replication stress.
2-hydroxypropanoic acid decreases the amount of USP20. 1 / 1
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ctd
No evidence text available
17alpha-ethynylestradiol decreases the amount of USP20. 1 / 1
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ctd
No evidence text available
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VDU1, but not VDU2, is markedly increased in brown adipocytes by norepinephrine or cold exposure, further amplifying the increase in D2 activity that results from catecholamine stimulated de novo synthesis.
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(+)-JQ1 compound increases the amount of USP20. 1 / 1
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ctd
No evidence text available