USP16 Data Analysis

HGNC Gene Name
ubiquitin specific peptidase 16
HGNC Gene Symbol
USP16
Identifiers
hgnc:12614 NCBIGene:10600 uniprot:Q9Y5T5
Orthologs
mgi:1921362 rgd:1307192
INDRA Statements
deubiquitinations all statements
Pathway Commons
Search for USP16
Number of Papers
62 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
TMEM50B transmembrane protein 50B 0.247
SETD4 SET domain containing 4 0.239
MNS1 meiosis specific nuclear structural 1 0.23
KRTAP20-1 keratin associated protein 20-1 0.228
RIPPLY3 ripply transcriptional repressor 3 0.22
CHODL chondrolectin 0.208
RWDD2B RWD domain containing 2B 0.207 0.15 0.75 4.81e-02

Dependency GO Term Enrichment

Gene set enrichment analysis was done on the genes correlated with USP16using 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 USP16 using CRISPR-Cas9.

Knockout Differential Expression

Symbol Name log2-fold-change p-value p-value (adj.)
S100A6 S100 calcium binding protein A6 6.54e-01 2.42e-14 3.27e-10
RPLP1 ribosomal protein lateral stalk subunit P1 9.83e-01 1.23e-11 8.33e-08
RPS12 ribosomal protein S12 1.20e+00 1.34e-09 6.05e-06
RPLP2 ribosomal protein lateral stalk subunit P2 7.57e-01 2.19e-09 7.40e-06
RPS28 ribosomal protein S28 9.62e-01 5.99e-07 1.62e-03
RPL7A ribosomal protein L7a 7.12e-01 4.95e-06 1.12e-02
RPS9 ribosomal protein S9 1.05e+00 1.02e-05 1.96e-02
RPS15A ribosomal protein S15a 6.85e-01 1.27e-05 2.15e-02
RPS28P7 ribosomal protein S28 pseudogene 7 9.05e-01 4.31e-05 4.85e-02
RPS4X ribosomal protein S4 X-linked 8.40e-01 4.26e-05 4.85e-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 USP16 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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USP16 deubiquitinates PLK1. 8 / 8
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ubiquitinspecific peptidase 16 (Usp16) was identified as a PLK1 interacting protein in a co-immunoprecipitation (co-IP) assay in a PBD-dependent manner

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Because Usp16 deubiquitinates Plk1, we wondered whether Plk1 mediated Usp16 activation would also enhance the deubiquitination of Plk1 itself.

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When Usp16 was knocked down by siRNA, we found that the ladder pattern bands above the main Plk1 band were enhanced, confirming our previous speculation that Usp16 might deubiquitinate Plk1 (XREF_FIG).

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In this study, we show that ubiquitin specific peptidase 16 (Usp16) is a novel substrate for Plk1, and sequential phosphorylation by CDK1 and Plk1 activates Usp16, which, in turn, deubiquitinates Plk1 and promotes the recruitment of Plk1 to, and its retention on, the kinetochores for proper chromosome alignment.

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Collectively, these results suggest that Plk1 is ubiquitinated by CUL3 based ubiquitin ligase in vivo, and the ubiquitination of Plk1 could be reversed by Usp16, which interacts with Plk1 in a PBD dependent manner in early mitosis.

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CDK1 and Plk1 sequentially phosphorylate and activate Usp16, which in turn deubiquitinates Plk1 to maintain the kinase 's kinetochore localization and promote proper chromosome alignment in mitosis.

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Usp16 interacts with and deubiquitinates Plk1.

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Usp16 deubiquitinates Plk1, resulting in an enhanced interaction with kinetochore localized proteins such as BubR1, and thereby retains Plk1 on the kinetochores to promote proper chromosome alignment in early mitosis.
USP16 deubiquitinates MYC. 2 / 2
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USP16 deubiquitinates c-Myc.

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Besides, the knockdown of USP16 significantly enhanced the polyubiquitination of c-Myc.
USP16 deubiquitinates Histone_H2B on lysine. 1 / 1
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USP16 specifically deubiquitinates histone H2A on lysine (K) 119 and K15 but not H2B in vivo, which leads to subsequent phosphorylation of H3 and chromosome segregation.
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USP16 deubiquitinates H2AC20. 1 / 1
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No evidence text available
USP16 deubiquitinates NANOG. 1 / 1
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USP16 deubiquitinates H2AW on K120. 1 / 1
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No evidence text available
USP16 deubiquitinates H2AC17. 1 / 1
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USP3 and USP16 function to remove ubiquitin from histone H2A during the DDR

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
PLK1 affects USP16
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PLK1 activates USP16. 7 / 11
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Because Usp16 deubiquitinates Plk1, we wondered whether Plk1 mediated Usp16 activation would also enhance the deubiquitination of Plk1 itself.

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These results suggest that Plk1 activates Usp16, which, in turn, deubiquitinates Plk1 itself.

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We found that the level of ubiquitinated histone H2A (ubH2A) was high in interphase and low in mitotic HeLa cells (Fig. S3, C–E), suggesting that Plk1 phosphorylates and activates Usp16.

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Plk1 phosphorylates and activates Usp16.

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These results suggest that Plk1 activates Usp16, which, in turn, deubiquitinates Plk1 itself.

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These results strongly suggest that Plk1 phosphorylates and activates Usp16, but the exact molecular mechanism of the activation is not clear at the moment.

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CDK1 and Plk1 sequentially phosphorylate and activate Usp16, which in turn deubiquitinates Plk1 to maintain the kinase’s kinetochore localization and promote proper chromosome alignment in mitosis.
USP16 affects PLK1
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USP16 activates PLK1.
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USP16 activates PLK1. 1 / 4
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Thus, our data unveil a unique mechanism by which Usp16 promotes the localization and maintenance of Plk1 on the kinetochores for proper chromosome alignment.
USP16 increases the amount of PLK1.
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USP16 increases the amount of PLK1. 3 / 3
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We found that, whereas the kinetochore localization of BubR1 was unchanged in both the control and Usp16 knockdown HeLa cells, knockdown of Usp16 in the cells reduced the amount of Plk1 localized on the kinetochores (XREF_FIG) and the binding between Plk1 and BubR1 (XREF_FIG).

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It was found that the WT and 3E, but not 3A, Usp16 could restore the level of kinetochore localized Plk1, which was initially reduced by Usp16 knockdown (XREF_FIG).

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Because the kinetochore localization of Plk1 is necessary for kinetochore-microtubule attachment and subsequent chromosome alignment, we speculated that suppression of Usp16, i.e., reducing the amount of Plk1 on the kinetochores, would delay the chromosome alignment and anaphase onset.

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A deubiquitylation enzyme, USP16, negatively regulates uH2A dependent function and rapidly restores transcription after the cessation of DNA damage.

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MYSM1 and USP16 activate transcription.

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Similar data were obtained with three separate siRNAs directed against USP16, while expression of a siRNA resistant USP16 allele restored transcription after ATMi (XREF_SUPPLEMENTARY).

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USP16 activates transcription of HOX genes in a manner consistent with reversing the repressive activity of the Polycomb complex.

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MYSM1 and USP16 activate transcription.

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USP16 depletion could prevent ATMi mediated restoration of transcription, indicating that this DUB is responsible for de-ubiquitylation of uH2A at DSBs.
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Moreover, Usp16 is associated with decreased ubiquitination of Cdkn2a and accelerated senescence in Ts65Dn fibroblasts.

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In hematopoietic stem cells, Usp16 over expression prematurely induces senescence via p16 Ink4a expression 10.

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In addition, Usp16 is associated with decreased ubiquitination of Cdkn2a and accelerated senescence in Ts65Dn fibroblasts.

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Collectively, USP11 has been clearly linked to essential DDR mechanisms and oncogene-induced senescence, highlighting it as a potentially attractive target for therapeutic agents.In a similar manner to USP3, USP16 has been characterised as an enzyme removing ubiquitin from histone H2A and involved in regulating the RNF8-RNF168 pathway [118] .
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The deubiquitinating enzyme USP16 suppresses self-renewal and senescence pathways in multiple tissues via deubiquitinating H2AK119 and increasing Ink4a locus transcription [XREF_BIBR], while BMI-1 regulates cell cycle, apoptosis and senescence via inhibiting p16 Ink4a and p19 Arf genes encoded by Ink4a [XREF_BIBR, XREF_BIBR].

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In this way, USP16 antagonizes the self-renewal and senescence pathways in multiple tissues.
USP16 affects cell growth
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USP16 activates cell growth.
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Indeed a knockdown of USP16 or an over-expression of its catalytically inactive form slow down cell growth and interfere with mitosis, suggesting that USP16 is the H2A-DUB responsible for histone H2A [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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Cells proliferation were then analysed using a CCK-8 assay, and the results revealed that knockdown of USP16 markedly reduced cell growth in PCa cells.

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These results demonstrate that inhibiting USP16 significantly suppressed PCa cell growth in vivo.

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Depletion of USP16 significantly increased the cell growth rate and inhibited cell anoikis in vitro (XREF_FIG and XREF_SUPPLEMENTARY).
USP16 inhibits cell growth.
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Downregulation of USP16 markedly suppressed PCa cell growth both in vitro and in vivo.

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In addition, USP16 overexpression in normal human fibroblasts and neural progenitors led to reduced cell expansion 159 , which was similar to the strong proliferation defects observed in fibroblasts from individuals with Down syndrome 160 .
USP16 affects CDKN2A
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USP16 activates CDKN2A.
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USP16 activates CDKN2A. 4 / 4
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USP16 activates Cdkn2a , which acts as a negative regulator of the Wnt signalling pathway .

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USP16 activates Cdkn2a, which acts as a negative regulator of the Wnt signalling pathway.

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Modulation of Ink4a and Arf by Usp16 in Ts65Dn cells.

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USP16 activates Cdkn2a, which acts as a negative regulator of the Wnt signalling pathway.
USP16 increases the amount of CDKN2A.
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Modified USP16 increases the amount of CDKN2A. 1 / 1
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In Ts65Dn satellite cells, Usp16 expression is increased but we found no evidence of increased p16 Ink4a expression (data not shown).
USP16 decreases the amount of CDKN2A.
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USP16 decreases the amount of CDKN2A. 1 / 1
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However, lentiviral downregulation of Usp16 with two different hairpins decreased p16 Ink4a and p19 Arf expression (XREF_FIG).
USP16 affects oxalate(1-)
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USP16 decreases the amount of oxalate(1-).
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USP16 decreases the amount of oxalate(1-). 2 / 2
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Given that previous studies indicate that H2A ubiquitination regulates Hox gene silencing, it is possible that Usp16 may repress Hox gene expression by modulating the levels of uH2A at the promoter and 5 ' end regulatory region of the Hox gene Finally, there is recent evidence that, in addition to a role in silencing, uH2A may also control transcriptional initiation.

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Knockdown of Usp16 causes a decrease in Hox expression and the rescue from this defect requires the deubiquitinating activity of Usp16.
USP16 activates oxalate(1-).
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Knockdown of Usp16 causes a decrease in Hox expression and the rescue from this defect requires the deubiquitinating activity of Usp16 .

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The in vivo relevance of Ubp-M mediated Hox gene activation was suggested by the observation that injection of Ubp-M antibodies in Xenopus embryos led to deregulation of HoxD10 expression and defects in posterior development.
USP16 inhibits oxalate(1-).
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Given that previous studies indicate that H2A ubiquitination regulates Hox gene silencing , it is possible that Usp16 may repress Hox gene expression by modulating the levels of uH2A at the promoter and 5 ' end regulatory region of the Hox gene ( 83 , 153 , 174 , 175 ) Finally , there is recent evidence that , in addition to a role in silencing , uH2A may also control transcriptional initiation .
USP16 increases the amount of oxalate(1-).
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USP16 increases the amount of oxalate(1-). 1 / 1
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USP16 activates transcription of HOX genes in a manner consistent with reversing the repressive activity of the Polycomb complex.

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Finally, Usp16, but not a catalytically inactive mutant, rescues the differentiation defects of Usp16 -/- ESCs.

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Wild-type Usp16 rescues Usp16 -/- ESC differentiation defect.

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When ESCs are differentiated, Usp16 is required to reverse ubH2A mediated gene repression and enables gene activation and subsequent ESC differentiation.

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Usp16 regulates H2A deubiquitination and modulates self-renewal and differentiation in different types of cells.

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Finally, we demonstrate that Usp16, but not the enzymatically inactive mutant, rescues the differentiation defects of Usp16 -/- ESCs.
CDK1 affects USP16
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CDK1 activates USP16. 2 / 5
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Here, we report that cyclin-dependent kinase 1 (cdk1) phosphorylates the histone h2a deubiquitinase ubp-m at serine 552 (s552p), and, importantly, this phosphorylation is required for cell cycle progression.

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CDK1 and Plk1 sequentially phosphorylate and activate Usp16, which in turn deubiquitinates Plk1 to maintain the kinase’s kinetochore localization and promote proper chromosome alignment in mitosis.
USP16 affects MYC
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USP16 activates MYC.
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USP16 activates MYC. 2 / 2
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We found that knockdown of USP16 dramatically reduced c-Myc protein abundance but did not affect its mRNA levels, suggesting that the regulation of c-Myc by USP16 occurs at the post-transcriptional level.

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We found that ectopic expression of USP16 enhanced the stability of c-Myc protein, while USP16 knockdown reduced the half-life of c-Myc protein.
USP16 activates MYC. 2 / 2
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Analysis of c-Myc protein levels by Western blot revealed that knockdown of USP16 significantly decreased the abundance of c-Myc.

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In addition, knockdown of USP16 significantly reduced c-Myc abundance at the post-translational level, while overexpression of wild-type USP16, instead of its catalytic inactive mutant (C205S) [XREF_BIBR], stabilized c-Myc.
USP16 decreases the amount of MYC.
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USP16 decreases the amount of MYC. 1 / 1
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In the present study, we found that the targeted disruption of USP16, but not other deubiquitinases of c-Myc, reduced c-Myc protein levels in PCa, indicating that DUBs have different functions in different cancers.

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Depletion of USP16 was shown to significantly suppress the growth of PCa cells both in vitro and in vivo.

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Downregulation of USP16 markedly suppressed PCa cell growth both in vitro and in vivo.

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USP16 knockdown suppresses growth of PCa tumour xenografts.

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These results demonstrate that inhibiting USP16 significantly suppressed PCa cell growth in vivo.

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Furthermore, in human tissues overexpression of USP16 reduces the expansion of normal fibroblasts and postnatal neural progenitors, whereas downregulation of USP16 partially rescues the proliferation defects of Down 's syndrome fibroblasts.

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Concordantly, we found that ectopic expression of USP16 mostly restored the proliferation rate of USP16 knockdown cells.

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Furthermore, in human tissues overexpression of USP16 reduces the expansion of normal fibroblasts and post-natal neural progenitors while downregulation of USP16 partially rescues the proliferation defects of DS fibroblasts.

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USP16 is upregulated in Down 's syndrome (DS) cells due to extrachromosomal triplication in trisomy 21, downregulation of USP16 partially restores the impaired proliferation in DS somatic stem cells.
USP16 affects Wnt
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USP16 activates Wnt. 3 / 3
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Usp16 copy number normalization restores normal Wnt activation in Ts65Dn mice models.

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Here we report that Usp16, a negative regulator of Bmi1 and PRC1 function, modulates the Wnt pathway in mammary epithelia, primary human fibroblasts and MEFs, affecting their expansion and self-renewal potential.

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Usp16 modulates Wnt signaling in primary tissues through Cdkn2a regulation.
USP16 affects NFkappaB
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USP16 activates NFkappaB.
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This result indicates a clear pivotal effect of myeloid USP16 mediated canonical NF-kappaB in experimental colitis model establishment and CRC development.
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In addition, transfection of USP16 WT, but not USP16 CI, increased TNF-alpha-induced NF-kappaB activity in HEK293T cells, as demonstrated by NF-kappaB luciferase reporter assays (XREF_FIG and fig.
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USP16 inhibits NFkappaB.
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Notably, USP16 deficiency greatly impaired the activation of NF-kappaB induced by TNF-alpha (XREF_FIG).
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USP16 affects NFKB1
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USP16 inhibits NFKB1.
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USP16 inhibits NFKB1. 2 / 2
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We further demonstrated that loss of USP16 specifically causes inactivation of p105 in both BMDMs and MEFs, as indicated by low phosphorylation levels of p105 and low nuclear translocation of p50.
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USP16 deficiency strongly inhibited the activation of p105 by the typical IKK complex under LPS stimulation, as revealed by an in vitro kinase assay (XREF_FIG).
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USP16 activates NFKB1.
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USP16 activates NFKB1. 1 / 1
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We further demonstrated that loss of USP16 specifically causes inactivation of p105 in both BMDMs and MEFs , as indicated by low phosphorylation levels of p105 and low nuclear translocation of p50 .
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USP16 affects DNA Damage
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USP16 activates DNA Damage.
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Overexpression of USP16 may induce excessive DNA damage accumulation, leading to acquisition of prematurely senescent phenotypes in different DS cell types [272, 274].

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Thus, the increased Usp16 expression in TS65Dn satellite cells could disrupt DNA repair, induce DNA damage, and impair satellite cell expansion.
USP16 inhibits DNA Damage.
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Since elevated Usp16 expression contributes to somatic stem cell dysfunction in Down syndrome 10 and Usp16 represses DNA damage responses XREF_BIBR, XREF_BIBR, we asked if Ts65Dn satellite cells accumulate more DNA damage that wild type satellite cells.
MYC affects USP16
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MYC inhibits USP16.
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MYC inhibits USP16. 1 / 1
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Co-immunoprecipitation and ubiquitination assays confirmed that USP16 served as a novel deubiquitinase of c-Myc and overexpression of c-Myc significantly rescued the effects of USP16 disruption.
MYC increases the amount of USP16.
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MYC increases the amount of USP16. 1 / 1
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Besides, it remains to explore whether c-Myc signalling could activate USP16 expression, resulting in a positive feedback loop that further promotes tumourigenesis.
MYC activates USP16.
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MYC activates USP16. 1 / 1
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Moreover, c-Myc overexpression restored the proliferation and colony formation abilities of USP16 silenced cells.
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Cyclosporin A increases the amount of USP16. 2 / 2
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USP16 affects proteolysis
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TTK dependent phosphorylation of Usp16 causes protein degradation.

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RT-PCR with Usp16 specific primers confirmed equivalent mRNA expression, suggesting that Usp16 phosphorylation promotes protein degradation.
USP16 affects PRC1
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USP16 inhibits PRC1. 2 / 2
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Interestingly, USP16, which is located on human chromosome 21 and triplicated in Down 's syndrome, reduces the self-renewal of hematopoietic stem cells and the expansion of mammary epithelial cells, neural progenitors and fibroblasts in mice, suggesting that Usp16 may antagonize PRC1 function in the self-renewal and/or senescence pathways 31.

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Since Bmi1 is known to be critical for the maintenance of neural progenitors XREF_BIBR, XREF_BIBR, XREF_BIBR, we hypothesized that an extra copy of the PRC1 antagonist Usp16 could have a role in regulating also their expansion in Ts65Dn mice.
Lipopolysaccharide increases the amount of USP16.
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Lipopolysaccharide increases the amount of USP16. 1 / 1
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Furthermore, LPS and TNFalpha, strong activators of the NFkappaB pathway, upregulated the USP16 transcription.
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Furthermore, we observed significant reductions in nuclear p50 levels and small decreases in nuclear translocated c-Rel and p65 levels in LPS stimulated USP16 deficient BMDMs (XREF_FIG).
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Bisphenol A affects USP16
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Bisphenol A increases the amount of USP16.
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Bisphenol A increases the amount of USP16. 1 / 1
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Bisphenol A decreases the amount of USP16.
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Bisphenol A decreases the amount of USP16. 1 / 1
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USP16 affects MKI67
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USP16 increases the amount of MKI67.
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USP16 increases the amount of MKI67. 1 / 1
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IHC staining analysis of the xenograft tissues revealed that inhibiting USP16 reduced Ki67 expression, indicating USP16 knockdown impaired the proliferation of PCa cells.
USP16 activates MKI67.
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USP16 activates MKI67. 1 / 1
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IHC staining analysis of the xenograft tissues revealed that inhibiting USP16 reduced Ki67 expression , indicating USP16 knockdown impaired the proliferation of PCa cells ( Fig. 3d-f ) .
USP16 affects HOXD10
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USP16 increases the amount of HOXD10.
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USP16 increases the amount of HOXD10. 1 / 1
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Furthermore inhibition of USP16 activity in vivo in Xenopus embryos similarly reduced HoxD10 gene expression, and resulted in abnormalities in the anterior-posterior patterning of the embryos (Joo et [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
USP16 decreases the amount of HOXD10.
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USP16 decreases the amount of HOXD10. 1 / 1
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Knockdown of USP16 or an over-expression of its catalytically inactive form in cell lines increased H2AK119Ub levels both globally and at the HoxD10 locus, and suppressed HoxD10 gene expression (Cai e[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
USP16 affects DNA repair
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USP16 inhibits DNA repair.
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Thus, the increased Usp16 expression in TS65Dn satellite cells could disrupt DNA repair, induce DNA damage, and impair satellite cell expansion.
USP16 activates DNA repair.
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USP16 bound to HERC2 activates DNA repair. 1 / 1
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USP16 interacts with HERC2 and modulates the ubiquitination in DNA repair machinery components.
USP16 affects DHPS
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USP16 inhibits DHPS.
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USP16 inhibits DHPS. 1 / 1
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USP16 is upregulated in Down 's syndrome (DS) cells due to extrachromosomal triplication in trisomy 21, downregulation of USP16 partially restores the impaired proliferation in DS somatic stem cells.
USP16 activates DHPS.
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USP16 activates DHPS. 1 / 1
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Furthermore, in human tissues overexpression of USP16 reduces the expansion of normal fibroblasts and post-natal neural progenitors while downregulation of USP16 partially rescues the proliferation defects of DS fibroblasts.
Proteasome affects USP16
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Proteasome inhibits USP16.
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Taken together, these data suggest that Usp16 is a phosphorylation substrate of TTK and that Usp16 phosphorylation on S415, S552, or T554 leads to proteasome degradation of Usp16.
Proteasome decreases the amount of USP16.
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Proteasome decreases the amount of mutated USP16. 1 / 1
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Inhibition of the proteasome with 10 muM MG-132 restored expression of the phosphomimetic Usp16 mutant (XREF_FIG).

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To identify whether USP16 serves as a DUB of c-Myc, HEK293T cells were transfected with plasmids encoding HA-ubiquitin and Flag-c-Myc with wild-type USP16 or its catalytically inactive mutant USP16 C205S and treated with MG132.

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To identify whether USP16 serves as a DUB of c-Myc, HEK293T cells were transfected with plasmids encoding HA-ubiquitin and Flag-c-Myc with wild-type USP16 or its catalytically inactive mutant USP16 C205S and treated with MG132.
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Valproic acid decreases the amount of USP16. 1 / 1
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Tungsten affects USP16
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Tungsten decreases the amount of USP16. 1 / 1
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Thimerosal affects USP16
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Thimerosal increases the amount of USP16. 1 / 1
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Tetrachloromethane increases the amount of USP16. 1 / 1
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Tert-butyl hydroperoxide increases the amount of USP16. 1 / 1
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Succimer affects USP16
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Succimer increases the amount of USP16. 1 / 1
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Streptozocin increases the amount of USP16. 1 / 1
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Sodium arsenite increases the amount of USP16. 1 / 1
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Silver(0) affects USP16
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Silver(0) increases the amount of USP16. 1 / 1
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Schizandrin B increases the amount of USP16. 1 / 1
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Propiconazole increases the amount of USP16. 1 / 1
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Progesterone increases the amount of USP16. 1 / 1
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Piroxicam affects USP16
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Piroxicam increases the amount of USP16. 1 / 1
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Methyl methanesulfonate increases the amount of USP16. 1 / 1
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Methamphetamine decreases the amount of USP16. 1 / 1
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Magnetite nanoparticle increases the amount of USP16. 1 / 1
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Jinfukang affects USP16
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Jinfukang decreases the amount of USP16. 1 / 1
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Ionomycin affects USP16
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Ionomycin increases the amount of USP16. 1 / 1
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Hypochlorous acid increases the amount of USP16. 1 / 1
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ctd
No evidence text available
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Hsa-miR-93-5p decreases the amount of USP16. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-519d-3p decreases the amount of USP16. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-324-5p decreases the amount of USP16. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-320a decreases the amount of USP16. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-30a-5p decreases the amount of USP16. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-20b-5p decreases the amount of USP16. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-20a-5p decreases the amount of USP16. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-182-5p decreases the amount of USP16. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-17-5p decreases the amount of USP16. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-106b-5p decreases the amount of USP16. 1 / 1
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biopax:mirtarbase
No evidence text available
Haloperidol affects USP16
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Haloperidol increases the amount of USP16. 1 / 1
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ctd
No evidence text available
Hairpins affects USP16
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Hairpins decreases the amount of USP16. 1 / 1
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These hairpins reduce Usp16 expression to 40-50% leading to a final expression level similar to the one observed in control animals (XREF_SUPPLEMENTARY).
Gold atom affects USP16
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Gold atom decreases the amount of USP16. 1 / 1
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ctd
No evidence text available
Esculetin affects USP16
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Esculetin increases the amount of USP16. 1 / 1
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ctd
No evidence text available
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ctd
No evidence text available
Dieldrin affects USP16
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Dieldrin increases the amount of USP16. 1 / 1
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ctd
No evidence text available
Dicrotophos affects USP16
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Dicrotophos decreases the amount of USP16. 1 / 1
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ctd
No evidence text available
Copper(II) sulfate increases the amount of USP16. 1 / 1
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ctd
No evidence text available
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Cobalt dichloride increases the amount of USP16. 1 / 1
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ctd
No evidence text available
Cadmium dichloride increases the amount of USP16. 1 / 1
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ctd
No evidence text available
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Cadmium atom decreases the amount of USP16. 1 / 1
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ctd
No evidence text available
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Benzo[a]pyrene decreases the amount of USP16. 1 / 1
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ctd
No evidence text available
Benzene affects USP16
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Benzene decreases the amount of USP16. 1 / 1
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ctd
No evidence text available
Atrazine affects USP16
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Atrazine increases the amount of USP16. 1 / 1
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ctd
No evidence text available
USP16 increases the amount of p-tolyl beta-D-glucuronide. 1 / 1
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Histone deubiquitination has been the subject of recent reviews [XREF_BIBR, XREF_BIBR, XREF_BIBR], and here we highlight three DUBs, USP7, USP16, and BAP1, that function in polycomb group (PcG) complexes and modulate transcription of PcG target genes.
USP16 affects mitosis
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USP16 activates mitosis. 1 / 1
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Usp16 regulates kinetochore localization of Plk1 to promote proper chromosome alignment in mitosis.
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Thus, our data unveil a unique mechanism by which Usp16 promotes the localization and maintenance of Plk1 on the kinetochores for proper chromosome alignment.
USP16 increases the amount of lipopolysaccharide. 1 / 1
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Furthermore, LPS and TNFalpha, strong activators of the NFkappaB pathway, upregulated the USP16 transcription.
USP16 affects VIM
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USP16 increases the amount of VIM. 1 / 1
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As shown in XREF_FIG, expression of the Igf2, Vimentin, Gata4, Gata6, and Foxa2 genes was significantly increased in EBs formed from Usp16 -/- ESCs rescued by wild-type Usp16.
USP16 affects Ubiquitin
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USP16 increases the amount of Ubiquitin. 1 / 1
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Ubiquintation of histone 2A at sites of DNA damage recruits DNA damage repair proteins, while Usp16 and other de-ubiquintases restore ubiquitin levels to normal approximately 24h after damage XREF_BIBR - XREF_BIBR.
USP16 affects USP16
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USP16 activates USP16. 1 / 1
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Concordantly, we found that ectopic expression of USP16 mostly restored the proliferation rate of USP16 knockdown cells.
USP16 affects TNF
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USP16 increases the amount of TNF. 1 / 1
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Furthermore, LPS and TNFalpha, strong activators of the NFkappaB pathway, upregulated the USP16 transcription.
USP16 affects RNF8
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USP16 activates RNF8. 1 / 1
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Whether USP16 targets the products of RNF8 and RNF168- and/or BMI1 and RING1B dependent ubiquitylation remains to be established.
USP16 affects RNF168
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USP16 activates RNF168. 1 / 1
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Whether USP16 targets the products of RNF8 and RNF168- and/or BMI1 and RING1B dependent ubiquitylation remains to be established.
USP16 affects LIN
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USP16 activates LIN. 1 / 1
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Like HSCs, Usp16 mRNA expression was increased approximately 1.5 fold in Ts65Dn CD49f + CD24 med Lin - cells compared to control cells (XREF_SUPPLEMENTARY).
USP16 affects IKBKB
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USP16 activates IKBKB. 1 / 1
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USP16 mediated DUB of IKKbeta directly, while the USP16 CI mutant lost its ability to regulate IKKbeta ubiquitination, as suggested by in vitro DUB assays (XREF_FIG).
| PMC
USP16 affects IGF2
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USP16 increases the amount of IGF2. 1 / 1
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As shown in XREF_FIG, expression of the Igf2, Vimentin, Gata4, Gata6, and Foxa2 genes was significantly increased in EBs formed from Usp16 -/- ESCs rescued by wild-type Usp16.
USP16 affects His2A
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USP16 activates His2A. 1 / 1
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Several independent pieces of data suggest a functional relationship between uH2A levels and DISC : (i) expression of an H2A allele that can not be monoubiquitylated at lysine 119 partially rescues transcription (XREF_FIG), (ii) inhibition of the known H2A E3 ubiquitin ligase RNF8 and the related RNF168 partially reverses silencing (XREF_FIG), and (iii) depletion of the uH2A deubiquitylating enzyme USP16 prevents the reversal of silencing and diminution of uH2A at DSBs upon ATMi or cessation of damage.
USP16 affects GATA6
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USP16 increases the amount of GATA6. 1 / 1
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As shown in XREF_FIG, expression of the Igf2, Vimentin, Gata4, Gata6, and Foxa2 genes was significantly increased in EBs formed from Usp16 -/- ESCs rescued by wild-type Usp16.
USP16 affects GATA4
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USP16 increases the amount of GATA4. 1 / 1
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As shown in XREF_FIG, expression of the Igf2, Vimentin, Gata4, Gata6, and Foxa2 genes was significantly increased in EBs formed from Usp16 -/- ESCs rescued by wild-type Usp16.
USP16 affects FOXA2
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USP16 increases the amount of FOXA2. 1 / 1
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As shown in XREF_FIG, expression of the Igf2, Vimentin, Gata4, Gata6, and Foxa2 genes was significantly increased in EBs formed from Usp16 -/- ESCs rescued by wild-type Usp16.
USP16 affects CUL3
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USP16 inhibits CUL3. 1 / 1
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Here, we showed that Usp16 antagonizes the activity of CUL3 based ubiquitin ligase by deubiquitinating Plk1, which not only promotes the localization of Plk1 to the kinetochores but also retains Plk1 there until metaphase.
USP16 affects CHAF1A
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USP16 activates CHAF1A. 1 / 1
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USP16 was confirmed as a direct target of miR-146a and USP16 overexpression in BM-MSCs abrogated the CLL-Exo-mediated up-regulation of CAF markers.
USP16 affects BCL2L1
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USP16 decreases the amount of BCL2L1. 1 / 1
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In accordance with this observation, we also found that knockdown of USP16 decreased P21 but increased Bcl-XL and Bcl -2 expression in liver tumour cells.
USP16 affects BCL2
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USP16 decreases the amount of BCL2. 1 / 1
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In accordance with this observation, we also found that knockdown of USP16 decreased P21 but increased Bcl-XL and Bcl -2 expression in liver tumour cells.
USP1 affects USP16
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USP1 activates USP16. 1 / 1
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In addition, DUBs involved in DNA damage signaling are USP1 that targets PCNA (proliferating cell nuclear antigen) [76], FANCD2 and FANCI (the Fanconi anemia proteins) [93,94], and USP3 and USP16 that[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
TNF affects USP16
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TNF increases the amount of USP16. 1 / 1
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Furthermore, LPS and TNFalpha, strong activators of the NFkappaB pathway, upregulated the USP16 transcription.
THAP1 affects USP16
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THAP1 decreases the amount of USP16. 1 / 1
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bel
Table 1. Genes regulated after ectopic expression of THAP1 in endothelial cells Genes down-regulated after ectopic expression of THAP1 in primary ECs
RELA affects USP16
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Modified RELA increases the amount of USP16. 1 / 1
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We showed that p65 overexpression enhanced endogenous USP16 mRNA level.
1 |
Plant Extracts increases the amount of USP16. 1 / 1
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ctd
No evidence text available
NFkappaB affects USP16
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NFkappaB increases the amount of USP16. 1 / 1
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Transcriptional activation of USP16 gene expression by NFkappaB signaling.
HERC2 affects USP16
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HERC2 increases the amount of USP16. 1 / 1
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In response to DNA damage, the HECT and RLD domain containing E3 ubiquitin protein ligase 2 (HERC2)-dependent increase in the level of USP16 negatively regulates ubiquitin foci formation by H2AK119Ub and K15Ub.
| PMC
1 |
Dietary Fats increases the amount of USP16. 1 / 1
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ctd
No evidence text available
1 |
D-glucopyranose increases the amount of USP16. 1 / 1
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ctd
No evidence text available
CDKN2A affects USP16
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CDKN2A activates USP16. 1 / 1
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Usp16 regulation of the Wnt pathway in mouse and human tissues is at least in part mediated by activation of Cdkn2a, a regulator of senescence.
3-methylcholanthrene increases the amount of USP16. 1 / 1
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ctd
No evidence text available
3-hydroxyisovaleric acid increases the amount of USP16. 1 / 1
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ctd
No evidence text available
2-hydroxypropanoic acid decreases the amount of USP16. 1 / 1
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ctd
No evidence text available
17alpha-ethynylestradiol increases the amount of USP16. 1 / 1
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ctd
No evidence text available