USP17L2 Data Analysis

HGNC Gene Name
ubiquitin specific peptidase 17 like family member 2
HGNC Gene Symbol
USP17L2
Identifiers
hgnc:34434 NCBIGene:377630 uniprot:Q6R6M4
Orthologs
rgd:6500127
INDRA Statements
deubiquitinations all statements
Pathway Commons
Search for USP17L2
Number of Papers
47 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 USP17L2using 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

Literature Mining

INDRA was used to automatically assemble known mechanisms related to USP17L2 from literature and knowledge bases. The first section shows only DUB activity and the second shows all other results.

Deubiquitinase Activity

psp cbn pc bel_lc signor biogrid lincs_drug tas hprd trrust ctd vhn pe drugbank omnipath conib crog dgi | rlimsp isi tees geneways eidos trips medscan sparser reach
USP17L2 deubiquitinates BRD4. 9 / 9
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Based on these genomic data and our finding that NCOR2 represses DUB3 expression in cultured cells, we hypothesized that loss of NCOR due to deletions or mutations results in DUB3 upregulation, which [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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Knockdown of DUB3 completely abolished NCOR2-depletion-induced elevation of BRD4 protein and BRD4 protein polyubiquitination but had no effect on BRD4 mRNA expression.

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In a recent study, DUB3 was shown to promote BRD4 deubiquitination and stabilization in various cancer cell lines [XREF_BIBR].

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Furthermore, PD0332991 treatment also increased BRD4 polyubiquitination, shortened the BRD4 protein half-life, and reversed DUB3 mediated deubiquitination of BRD4 in DU145 cells.

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In support of these findings, we show that inhibition of BRD4 by JQ1 blocks NCOR2 mRNA expression, which in turn dismisses NCOR2 mediated repression of DUB3 and DUB3 mediated deubiquitination of BRD4.

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In agreement with these findings, knockdown of DUB3 shortened the BRD4 protein half-life and dramatically increased endogenous BRD4 ubiquitination in PC-3 cells.

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DUB3 promotes BET inhibitor resistance and cancer progression by deubiquitinating BRD4.

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Here, we demonstrate that the deubiquitinase DUB3 binds to BRD4 and promotes its deubiquitination and stabilization.

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DUB3 Deubiquitinates BRD4 to Promote Prostate Cancer Progression.
USP17L2 deubiquitinates CDC25A. 4 / 4
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No evidence text available

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We also assessed the level of ubiquitin hydrolase DUB3 that is known to deubiquitylate and stabilize CDC25A 46.

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DUB3 and USP17 mediates deubiquitination of CDC25A, preventing CDC25A degradation by the proteasome during the G1/S and G2/M phases promoting cell-cycle progression [XREF_BIBR].

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Dub3 knockdown in cells increased Cdc25A ubiquitylation and degradation, resulting in reduced Cdk and Cyclin activity and arrest at G1/S and G2/M phases of the cell cycle.
USP17L2 deubiquitinates H2AX. 4 / 4
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Dub3 controls DNA damage signalling by direct deubiquitination of H2AX

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Moreover, Dub3 and H2AX interact and Dub3 deubiquitinates H2AX in vitro.

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DUB3 (also known as USP17L2) directly interacts with and deubiquitylates H2AX [73].

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Moreover, Dub3 and H2AX interact and Dub3 deubiquitinates H2AX in vitro.
USP17L2 deubiquitinates SUDS3. 2 / 2
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We previously reported that the USP17 deubiquitinating enzyme having hyaluronan binding motifs (HABMs) interacts with human SDS3 (suppressor of defective silencing 3) and specifically deubiquitinates Lys-63 branched polyubiquitination of SDS3 resulting in negative regulation of histone deacetylase (HDAC) activity in cancer cells.

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DUB-3 (also known as USP17) is a cytokine-inducible human DUB that was found to deubiquitinate SDS3 and block proliferation in HeLa cells [93].
USP17L2 deubiquitinates SNAI2. 2 / 2
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In this study, we identified Dub3 as a novel DUB for both Slug and Twist. We further found that Dub3 overexpression increased Slug and Twist protein levels in a dose-dependent manner, whereas Dub3-knockdown decreased their protein levels.

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Dub3 deubiquitinates Slug and Twist.
USP17L2 deubiquitinates TWIST1. 2 / 2
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In this study, we identified Dub3 as a novel DUB for both Slug and Twist. We further found that Dub3 overexpression increased Slug and Twist protein levels in a dose-dependent manner, whereas Dub3-knockdown decreased their protein levels.

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Dub3 deubiquitinates Slug and Twist.
USP17L2 deubiquitinates AMOT. 1 / 1
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Interestingly DUB3 also interacts with and deubiquitinates AMOT, AMOTL1, and the kinases LATS1 and LATS2 to promote their stability and in so doing decrease YAP activity [124].
Modified USP17L2 leads to the deubiquitination of AMOT. 1 / 1
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Reciprocally, overexpression of DUB3 reduced the ubiquitylation of AMOT, while the inactive C89S DUB3 mutant had no effect (XREF_SUPPLEMENTARY).
USP17L2 deubiquitinates RAS. 1 / 1
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DUB-3 also influenced the Ras/MEK/ERK signaling pathway and deubiquitinated Ras converting enzyme 1 (RCE1), decreasing proliferation of cells [XREF_BIBR].
USP17L2 deubiquitinates IFIH1. 1 / 1
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Taken together, our findings suggest that USP17 functions through deubiquitination of RIG-I and MDA5 to regulate virus-induced type I IFN signaling.
USP17L2 deubiquitinates HAS2. 1 / 1
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?Several DUBs were found to decrease the ubiquitination of 6myc-HAS2, among which, the most effective were USP17 and USP4. USP17 efficiently removed polyubiquitination, whereas USP4 preferentially removed monoubiquitination of 6myc-HAS2.
USP17L2 deubiquitinates DDX58. 1 / 1
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Taken together, our findings suggest that USP17 functions through deubiquitination of RIG-I and MDA5 to regulate virus-induced type I IFN signaling.
Modified USP17L2 leads to the deubiquitination of ITCH. 1 / 1
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Expression of DUB3 strongly reduced the amount of poly-ubiquitylated ITCH (XREF_FIG).
USP17L2 deubiquitinates AMOTL1. 1 / 1
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Interestingly DUB3 also interacts with and deubiquitinates AMOT, AMOTL1, and the kinases LATS1 and LATS2 to promote their stability and in so doing decrease YAP activity [124].
USP17L2 deubiquitinates SNAI1. 1 / 1
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CDK4/6-mediated activation of DUB3 is essential to deubiquitinate and stabilize SNAIL1
Modified USP17L2 leads to the deubiquitination of SNAI2. 1 / 1
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Co-expression of wild-type (WT) Dub3 almost completely abolished ubiquitination of Slug and Twist, while co-expression of CS-Dub3 did not show this effect (lane 2 vs lane 3 in both upper panels, Figure XREF_FIG).
USP17L2 deubiquitinates RCE1. 1 / 1
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we show that this effect is caused by the loss of RCE1 catalytic activity as a result of its deubiquitination by USP17.
USP17L2 deubiquitinates DELEC1. 1 / 1
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USP17 binds and deubiquitylates DEC1, markedly extending its half-life.
USP17L2 deubiquitinates LGMN. 1 / 1
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We demonstrate that TRAF6 ubiquitinates the proform of AEP through K63-linked polyubiquitin, reversible by USP17, and forms a complex with HSP90伪 to subsequently promote pro-AEP intracellular stability as well as secretion.?
USP17L2 deubiquitinates LATS2. 1 / 1
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Interestingly DUB3 also interacts with and deubiquitinates AMOT, AMOTL1, and the kinases LATS1 and LATS2 to promote their stability and in so doing decrease YAP activity [124].
Modified USP17L2 leads to the deubiquitination of LATS2. 1 / 1
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LATS2 ubiquitylation was markedly suppressed by overexpression of DUB3, but not by the catalytically inactive C89S form of DUB3 (XREF_SUPPLEMENTARY).
Modified USP17L2 leads to the deubiquitination of TWIST1. 1 / 1
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Co-expression of wild-type (WT) Dub3 almost completely abolished ubiquitination of Slug and Twist, while co-expression of CS-Dub3 did not show this effect (lane 2 vs lane 3 in both upper panels, Figure XREF_FIG).
USP17L2 deubiquitinates LATS1. 1 / 1
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Interestingly DUB3 also interacts with and deubiquitinates AMOT, AMOTL1, and the kinases LATS1 and LATS2 to promote their stability and in so doing decrease YAP activity [124].
USP17L2 deubiquitinates NFE2L2. 1 / 1
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DUB3 deubiquitinates and stabilizes NRF2 in chemotherapy resistance of colorectal cancer.
USP17L2 deubiquitinates ITCH. 1 / 1
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First, DUB3 deubiquitinates and stabilizes the E3 ligase ITCH.

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

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Dub-3, which is known as Usp17, is responsible for the regulation of cell growth and survival, and the constitutive expression of Dub-3 can block cell proliferation XREF_BIBR - XREF_BIBR.

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Knockdown of Dub3 could inhibit the proliferation of ovarian cancer cells and increase cell apoptosis.

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DUB-3, a cytokine inducible deubiquitinating enzyme that blocks proliferation.

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We originally showed that constitutive expression of DUB-3 can block cell proliferation and more recently we have demonstrated that this is due to its regulation of the ubiquitination and activity of the ' CAAX ' box protease RCE1.

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More recently, we have also reported that constitutive expression of DUB-3 can block cell proliferation [XREF_BIBR, XREF_BIBR] and subsequently we have demonstrated that this is due to its regulation of the ubiquitination and activity of the ' CAAX ' box protease Ras converting enzyme 1 (RCE1) [XREF_BIBR].

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The constitutive expression of DUB-3 can block cell proliferation and initiate apoptosis [25].

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In particular, DUB-1 expression results in cell cycle arrest prior to S-phase [XREF_BIBR], DUB-2 expression markedly inhibits apoptosis induced by cytokine withdrawal [XREF_BIBR] and we have previously reported that constitutive expression of DUB-3 blocks cell proliferation [XREF_BIBR, XREF_BIBR, XREF_BIBR] through its regulation of the ubiquitination and activity of the ' CAAX ' box protease RCE1 [XREF_BIBR, XREF_BIBR].

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Finally, we have demonstrated that constitutive expression of DUB-3 blocks proliferation and can initiate apoptosis in both IL-3-dependent Ba/F3 cells and NIH3T3 fibroblasts.

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USP17 subfamily members have been previously identified [XREF_BIBR] and one of them, DUB-3, has shown that the constitutive expression of DUB-3 blocks proliferation and can lead to apoptosis [XREF_BIBR].

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DUB3 promoted OSCC cells proliferation, while suppressing apoptosis via facilitating EZH2 production.

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Functionally, we found that the effect of DUB3 on cyclin A mediates proliferation of NSCLC cells.

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In summary, we found that DUB3 enhanced OSCC cells proliferation and xenograft tumor growth, while inhibited their apoptosis via promoting BRD4 mediated upregulation of EZH2.

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Similar to our observations, previous shRNA studies have also indicated that Dub3 knockdown reduces proliferation by inhibiting the G1-S phase cell cycle progression and inhibits chemotaxis [14,15,26][MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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In vitro, Dub3 knockdown could inhibit the proliferation of ovarian cancer cells and increase cell apoptosis.

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McFarlane et al. identify that USP17 is highly expressed in several tumor biopsies , and USP17 depletion significantly impairs G1-S phase transition and blocks cell proliferation ( 56 ) .
USP17L2 affects BRD4
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USP17L2 activates BRD4.
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USP17L2 activates BRD4. 6 / 6
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We demonstrated that knockdown of endogenous DUB3 by two independent shRNAs largely decreased BRD4 protein and that these effects were reversed by restored expression of DUB3-WT and the phospho mimick[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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We further showed that forced expression of DUB3 induced upregulation of BRD4 proteins in cultured cells and that elevation of DUB3 expression was correlated with a high level of BRD4 protein in a sub[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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Treatment of DU145 cells with PD0332991 decreased BRD4 protein levels in a time dependent manner, and the effect of PD0332991 was completely impeded by the proteasome inhibitor MG132, arguing that CDK[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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In contrast, knockdown of DUB3 by two independent shRNAs decreased the level of endogenous BRD4 proteins but had no overt effect on BRD4 mRNA expression in both PC-3 and DU145 cells.

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DUB3 mediated BRD4 stabilization overcomes SPOP mediated degradation to confer BET inhibitor resistance.

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Accordingly, overexpression of DUB3 increased the level of ectopically expressed full-length BRD4 protein in a dose dependent manner but had no effect on BRD4DeltaCTM mutant, BRD2 or BRD3 in PC-3 cell[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
USP17L2 increases the amount of BRD4.
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USP17L2 increases the amount of BRD4. 5 / 5
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Accordingly, DUB3 knockdown decreased BRD4 protein levels in F133V expressing cells, and this effect was blocked by MG132.

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In an array of cancer cell lines, we demonstrated that knockdown of DUB3 by shRNAs largely decreased BRD4 protein levels, but not at mRNA levels.

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To test this hypothesis, we co-expressed DUB3 with BRD4 in 293T cells and found that DUB3 increased BRD4 protein expression in a dose dependent manner.

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Unexpectedly, knockdown of DUB3 not only decreased BRD4 protein levels in SPOP F133V expressing DU145 cells but also sensitized SPOP-F133V cells to JQ1 treatment, suggesting the presence of a SPOP ind[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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Moreover, knockdown of DUB3 largely decreased BRD4 protein levels, but little or no further reduction in BRD4 protein expression by co-treatment with PD0332991 was observed.
USP17L2 inhibits BRD4.
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USP17L2 inhibits BRD4. 1 / 1
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We further demonstrated that downregulation of BRD4 proteins caused by DUB3 knockdown was reversed by treating cells with the proteasome inhibitor MG132.
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To directly assess whether Dub3 promotes metastasis in vivo, we intravenously injected Dub3-knockdown MDA-MB231 cells into female SCID mice and subjected these mice to bioluminescent imaging (BLI).

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Dub3 inhibition suppresses breast cancer invasion and metastasis by promoting Snail1 degradation.

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Dub3 knockdown after DOX treatment significantly decreased lung metastasis and lung weight, but these parameters showed no difference in control mice with or without DOX treatment (middle and right panels, XREF_FIG).

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USP17 Knockdown Impairs Tumor Proliferation and Metastasis Through Targeting MMPs Because degradation of the basement membrane by MMPs is required for tumor cell migration and invasion ( 16,17 ) , we sought to determine whether MMPs were responsible for USP17-dependent growth and invasion .

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Dub3 inhibition suppresses breast cancer invasion and metastasis by promoting Snail1 degradation.

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It has been reported that Snail1 pathway is involved in the progression of many diseases , for instance , Dub3 inhibition suppresses breast cancer invasion and metastasis by promoting Snail1 degradation.25 CLDN6 promotes tumor progression through the YAP1-snail1 axis in gastric cancer.26 Moreover , it has been reported that Snail1 has involved the progression of DN.27 Consistent with our research , mRNA and protein expression of Snail1 was decreased in PVT1-KD MCs , which was reversed by treating with miR-325-3p inhibitor .

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Dub3 is overexpressed in breast cancer; knockdown of Dub3 resulted in Snail1 destabilization, suppressed EMT and decreased tumour cell migration, invasion, and metastasis.

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Our results (shown in XREF_FIG and XREF_SUPPLEMENTARY) demonstrate DUB3 's ability to increase breast cancer cell migration and metastasis by targeting SNAIL1, thereby supporting our hypothesis that DUB3 promotes breast carcinoma metastasis in patients.

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Inhibition of USP17 promotes SNAI1 degradation , thereby suppressing breast cancer invasion and metastasis ( 49 , 53 ) .

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These experimental findings suggested that Dub3 potentially promoted cancer growth and metastasis.

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Knockdown of Dub3 blocks breast cancer metastasis.
NCOR2 affects USP17L2
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NCOR2 decreases the amount of USP17L2.
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NCOR2 decreases the amount of USP17L2. 5 / 5
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These data suggest that NCOR2 and HDAC10 work in concert in the same complex to repress expression of DUB3 in prostate cancer cells.

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Our current findings show that NCOR2, functioning as a transcriptional repressor, represses DUB3 expression.

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Based on these genomic data and our finding that NCOR2 represses DUB3 expression in cultured cells, we hypothesized that loss of NCOR due to deletions or mutations results in DUB3 upregulation, which [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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We demonstrated that NCOR2 represses DUB3 expression by specifically interacting with HDAC10.

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We found that knockdown of NCOR2 by two independent shRNAs increased expression of DUB3 and BRD4 proteins, but not BRD2 and BRD3 proteins, while NCOR2 knockdown increased mRNA expression of DUB3, but [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
NCOR2 bound to HDAC10 decreases the amount of USP17L2. 2 / 2
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Expression of DUB3 is transcriptionally repressed by the NCOR2 and HDAC10 complex.

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We also show that expression of DUB3 is negatively regulated by the NCOR2 and HDAC10 complex.
NCOR2 inhibits USP17L2.
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The NCOR2 gene is frequently deleted in castration resistant prostate cancer patient specimens, and loss of NCOR2 induces elevation of DUB3 and BRD4 proteins in cancer cells.

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Using a gain-of-function approach, we demonstrated that overexpression of BRD4 elevated NCOR2 expression but repressed DUB3 at both the mRNA and protein levels in C4-2 cells.
NCOR2 increases the amount of USP17L2.
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NCOR2 increases the amount of USP17L2. 1 / 1
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We provide evidence that depletion of NCOR2 by shRNAs increases DUB3 and BRD4 levels in prostate cancer cells in culture.
Modified NCOR2 increases the amount of USP17L2. 1 / 1
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Deletion of the NCOR2 gene was detected in a subset of CRPC patients, and loss of NCOR2 resulted in overexpression of DUB3 in prostate cancer cells.
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USP17 promotes proliferation and invasion through PI3K / AKT activation in NSCLC Consistent with the findings from the USP17-OE cells , knock-down ( KD ) of USP17 decreased the protein expression levels of p-AKT and p-PI3K in NSCLC cells ( NC vs. KD , P < 0.0001 ; Fig. 6A-F ) .

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Dub3 inhibition suppresses breast cancer invasion and metastasis by promoting Snail1 degradation.

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Suppression of Ubiquitin-Specific Peptidase 17 ( USP17 ) Inhibits Tumorigenesis and Invasion in Non-Small Cell Lung Cancer Cells USP17 PROMOTES TUMORIGENESIS AND METASTASIS IN NSCLC ZHANG , YUAN , AND ZHENG Recently , deubiquitinating enzymes ( DUBs ) are emerging as new regulators in cancer progression .

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Taken together , our study showed that USP17 promotes tumorigenesis and invasion through regulation of MMPs ( MMP3 and MMP9 ) in NSCLC cells and provides a promising approach for NSCLC treatment and prevention .

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Dub3 mediates migration, invasion and CSC like properties of breast cancer cells.

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Furthermore, we demonstrated that Dub3 promoted migration, invasion and CSC like properties of breast cancer cells.

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Dub3 is overexpressed in breast cancer; knockdown of Dub3 resulted in Snail1 destabilization, suppressed EMT and decreased tumour cell migration, invasion, and metastasis.

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Dub3 inhibition suppresses breast cancer invasion and metastasis by promoting Snail1 degradation.
USP17L2 bound to SNAI1 activates Neoplasm Invasiveness. 1 / 1
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By blocking the interaction of Dub3 and Snail, WP1130 prevents the deubiquitination of Snail, thereby blocking cancer invasion, migration, and the establishment of CSC like properties.

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Depletion of DUB3 significantly inhibited the migratory ability and invasiveness of MDA-MB-231 cells (XREF_FIG), although it did not affect cell proliferation (XREF_SUPPLEMENTARY).
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Finally, we have demonstrated that constitutive expression of DUB-3 blocks proliferation and can initiate apoptosis in both IL-3-dependent Ba/F3 cells and NIH3T3 fibroblasts.

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DUB3 and USP17 was reported to induce apoptosis through caspase-3 activation.

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In vitro, Dub3 knockdown could inhibit the proliferation of ovarian cancer cells and increase cell apoptosis.

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Several studies have examined the mechanism by which DUB-3 and USP17 induces apoptosis.

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The constitutive expression of DUB-3 can block cell proliferation and initiate apoptosis [25].
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DUB3 Facilitates Growth and Inhibits Apoptosis Through Enhancing Expression of EZH2 in Oral Squamous Cell Carcinoma.

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Furthermore, overexpression of Mcl-1 or DUB3 inhibited apoptosis by PTC596.

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Knockdown of Dub3 could inhibit the proliferation of ovarian cancer cells and increase cell apoptosis.

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Here our studies indicate that DUB3 is crucial to induce EMT through the stabilization of SNAIL1 protein in breast cancer.

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Consistently, Dub3 expression induced a morphologic change indicative of EMT (XREF_FIG), including downregulation of epithelial markers (E-cadherin, Claudin-7 and Occludin) and the upregulation of mesenchymal molecules (N-cadherin and Vimentin) (XREF_FIG, XREF_SUPPLEMENTARY).

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Together, these data indicate that Dub3 can induce EMT (luminal to basal like phenotype conversion) by stabilizing Snail1 in breast cancer cells.

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Dub3 expression induces EMT.

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Dub3 is overexpressed in breast cancer; knockdown of Dub3 resulted in Snail1 destabilization, suppressed EMT and decreased tumour cell migration, invasion, and metastasis.

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By contrast, ectopic expression of Dub3 induces EMT through an upregulation of Snail.
Cdk-4 affects USP17L2
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Cdk-4 activates USP17L2.
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Cdk-4 activates USP17L2. 5 / 5
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CDK4/6 dependent activation of DUB3 regulates cancer metastasis through SNAIL1.

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CDK4/6 mediated activation of DUB3 is essential to deubiquitinate and stabilize SNAIL1, a transcription factor that promotes epithelial-mesenchymal transition (EMT) and, therefore, invasiveness.

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Besides, CDK4/6 mediated activation of DUB3 has been reported to be essential to deubiquitinate and stabilize SNAIL1, a key factor promoting EMT and involved in breast cancer metastasis 34.

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CDK4/6-dependent activation of DUB3 regulates cancer metastasis through SNAIL1.

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CDK4/6 phosphorylates and activates DUB3.
Cdk-4 inhibits USP17L2.
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These data suggest DUB3 is a critical upstream regulator of BRD4 protein stability and that inhibition of DUB3 by CDK4/6 inhibitor overcomes BET-inhibitor-induced elevation of BRD4 protein and BET inh[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
IL6 affects USP17L2
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IL6 activates USP17L2.
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IL6 activates USP17L2. 5 / 5
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Interestingly, Dub3 activity and expression, at both the mRNA and protein levels, can be induced by IL-6 through the JAK and STAT3 signaling pathway [XREF_BIBR, XREF_BIBR, XREF_BIBR].

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In addition, the DUB-3 protein, induced by IL-4 and IL-6, is also involved in the regulation of cell growth and survival where its constitutive expression leads to growth suppression and apoptosis [25[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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In addition, Dub3 can be rapidly induced by inflammatory cytokine IL-6 [XREF_BIBR, XREF_BIBR].

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Specifically, Dub3 is rapidly induced by IL-4 and IL-6.

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Curiously, the DUB3 gene, a part of the highly polymorphic RS447 megasatellite sequence, is induced by cytokines interleukin (IL-) 4 and IL-6 in certain mammalian cells XREF_BIBR XREF_BIBR.
IL6 increases the amount of USP17L2.
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IL6 increases the amount of USP17L2. 1 / 1
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Consistent with this, we also found that IL-6 rapidly induces Dub3 expression, exerting a maximum effect at 2hr [XREF_BIBR].
ESRRB affects USP17L2
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ESRRB activates USP17L2.
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ESRRB activates USP17L2. 4 / 4
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ERRbeta knockdown in and DY131 stimulation of mouse ESCs reduces or enhances Dub3 and Cdc25A, respectively, and RNAi mediated inhibition of Dub3 or Cdc25A led these cells to differentiate.

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To address the specific role of the two splice variants NCoA and SRC1A and NCoA and SRC1E on Esrrb mediated Dub3 transcription, we individually cotransfected each coactivators with Esrrb and measured the activity of a luciferase reporter gene.

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Surprisingly, we also found an interaction through the Q rich domain, which seemed to convey inhibitory signals since deletion of this region resulted in increased Esrrb mediated Dub3 transcription (XREF_FIG).

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As expected, only wild type Esrrb and not the C-terminally truncated receptor increased Dub3 transcriptional activity (XREF_FIG), indicating that coactivator recruitment through the C-terminus that contains the AF2 domain is essential to the Esrrb mediated transcriptional response on the Dub3 promoter.
ESRRB decreases the amount of USP17L2.
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ESRRB decreases the amount of USP17L2. 1 / 1
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These findings further highlight the complexity of the regulatory network of transcription factors in pluripotent mESCs and may explain why downregulation of Esrrb does not completely abolish Dub3 gene expression in mESCs XREF_BIBR.
CPOX affects USP17L2
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CPOX increases the amount of USP17L2.
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CPOX increases the amount of USP17L2. 3 / 3
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Again, CPX did not reduce, but unexpectedly increased DUB3 protein expression slightly.

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Currently, we have no clue why and how CPX downregulated CK1alpha and upregulated DUB3 expression.

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On the contrary, CPX slightly increased the expression of DUB3 in a concentration dependent manner.
CPOX inhibits USP17L2.
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CPOX inhibits USP17L2. 1 / 1
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Since Cdc25A degradation is beta-TrCP ubiquitin dependent [XREF_BIBR, XREF_BIBR], next, we checked whether CPX downregulates DUB3, a Cdc25A specific deubiquitinase, which protects Cdc25A from degradation by removing ubiquitin chain from Cdc25A [XREF_BIBR].
CPOX decreases the amount of USP17L2.
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CPOX decreases the amount of USP17L2. 1 / 1
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As shown in Figures XREF_FIG and XREF_FIG, CPX did not reduce the protein level of DUB3.
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Individual cell tracking also revealed Dub3 knockdown reduced the velocity and directionality of cell migration, and strongly inhibited the net distance of cell migration in MDA-MB231 and MDA-MB157 cells (XREF_FIG, XREF_SUPPLEMENTARY).

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Moreover , Matrigel-Transwell analysis showed that suppression of USP17 decreased cell migration and invasion capacity .

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Dub3 is overexpressed in breast cancer; knockdown of Dub3 resulted in Snail1 destabilization, suppressed EMT and decreased tumour cell migration, invasion, and metastasis.

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Dub3 expression markedly increased the cell migration and invasive capacity (XREF_FIG, XREF_SUPPLEMENTARY).
USP17L2 affects NFE2L2
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Importantly, ectopic expression of DUB3 caused NRF2 dependent chemotherapy resistance in colon cancer cell lines.

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DUB3 promotes Nrf2 stability and transcriptional activity by decreasing the K48 linked ubiquitination of Nrf2.

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Further experiments demonstrated that DUB3 promoted NRF2 stability and transcriptional activity by decreasing the K48 linked ubiquitination of NRF2.

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Moreover, these authors demonstrated that ectopic expression of DUB3 caused Nrf2 dependent chemotherapy resistance in colon cancer cell lines [XREF_BIBR].
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Moreover , the in vivo animal models revealed that USP17 suppression reduced tumorigenesis and growth .

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Suppression of USP17 reduced tumorigenesis and progression of NSCLC in vivo .

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Taken together , our study showed that USP17 promotes tumorigenesis and invasion through regulation of MMPs ( MMP3 and MMP9 ) in NSCLC cells and provides a promising approach for NSCLC treatment and prevention .

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Suppression of Ubiquitin-Specific Peptidase 17 ( USP17 ) Inhibits Tumorigenesis and Invasion in Non-Small Cell Lung Cancer Cells USP17 PROMOTES TUMORIGENESIS AND METASTASIS IN NSCLC ZHANG , YUAN , AND ZHENG Recently , deubiquitinating enzymes ( DUBs ) are emerging as new regulators in cancer progression .
USP17L2 affects SNAI2
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USP17L2 increases the amount of SNAI2.
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Modified USP17L2 increases the amount of SNAI2. 2 / 2
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Expression of Dub3 in these two cell lines dramatically increased the levels of Slug and Twist and reduced E-cadherin and ER expression.

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We further found that Dub3 overexpression increased Slug and Twist protein levels in a dose dependent manner, whereas Dub3-knockdown decreased their protein levels.
USP17L2 increases the amount of SNAI2. 1 / 1
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When Dub3 was co-expressed with Slug in HEK293 cells, we found that Dub3 significantly increased protein levels of Slug, an effect comparable to treatment with proteasome inhibitor MG132 (top panel, Figure XREF_FIG).
USP17L2 activates SNAI2.
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USP17L2 activates SNAI2. 1 / 1
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To further define the mechanism of Dub3 mediated Slug and Twist stabilization, we performed co-immunoprecipitation (Co-IP) experiment using HEK293 cells expressing both Myc-Dub3 and Flag-Slug or HA-Twist.

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Furthermore, we demonstrated that Dub3 promoted migration, invasion and CSC like properties of breast cancer cells.

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Dub3 mediates migration, invasion and CSC like properties of breast cancer cells.
USP17L2 bound to SNAI1 activates Neoplastic Stem Cells. 1 / 1
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By blocking the interaction of Dub3 and Snail, WP1130 prevents the deubiquitination of Snail, thereby blocking cancer invasion, migration, and the establishment of CSC like properties.

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Knockdown of Dub3 inhibits migration, invasion and cancer stem cell (CSC)-like characteristics in cells by downregulating of Snail.
BRD4 affects USP17L2
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BRD4 inhibits USP17L2.
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BRD4 inhibits USP17L2. 2 / 2
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Using a gain-of-function approach, we demonstrated that overexpression of BRD4 elevated NCOR2 expression but repressed DUB3 at both the mRNA and protein levels in C4-2 cells.

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In contrast, knockdown of BRD4 by two independent shRNAs decreased NCOR2 but increased DUB3 mRNA and protein expression in both C4-2 and PC-3 cells.
BRD4 increases the amount of USP17L2.
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BRD4 increases the amount of USP17L2. 1 / 1
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Since we identified NCOR2 and HDAC10 as upstream repressors of DUB mRNA expression, we asked whether BRD4 modulates DUB3 expression by regulating NCOR2 and/or HDAC10.
BRD4 activates USP17L2.
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BRD4 activates USP17L2. 1 / 1
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Taken together, these data indicate that BRD4 induces downregulation of DUB3 through upregulation of NCOR2, which acts as a repressor of DUB3 transcription.
IL4 affects USP17L2
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IL4 activates USP17L2. 3 / 3
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In mRNA level, DUB-3 expression increased in Raji cells when treated with IL-4 and in U937 cells when treated with IL-6 [XREF_BIBR].

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In addition, the DUB-3 protein, induced by IL-4 and IL-6, is also involved in the regulation of cell growth and survival where its constitutive expression leads to growth suppression and apoptosis [25[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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Specifically, Dub3 is rapidly induced by IL-4 and IL-6.

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Finally, knockdown of either Dub3 or Cdc25A induced spontaneous differentiation of ESCs.

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This transcriptional control appears to be very complex and gene specific and remains to be further clarified.We observed that while forced Dub3 expression could not inhibit differentiation upon LIF w[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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Gene Expression Analysis of PTEN Positive Glioblastoma Stem Cells Identifies DUB3 and Wee1 Modulation in a Cell Differentiation Model.
USP17L2 affects TWIST1
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USP17L2 increases the amount of TWIST1.
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Modified USP17L2 increases the amount of TWIST1. 2 / 2
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We further found that Dub3 overexpression increased Slug and Twist protein levels in a dose dependent manner, whereas Dub3-knockdown decreased their protein levels.

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Expression of Dub3 in these two cell lines dramatically increased the levels of Slug and Twist and reduced E-cadherin and ER expression.
USP17L2 activates TWIST1.
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Surprisingly, Dub3 also significantly increased Twist protein (bottom panel, Figure XREF_FIG).
USP17L2 affects SNAI1
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USP17L2 activates SNAI1.
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USP17L2 activates SNAI1. 2 / 2
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Inhibition of USP17 promotes SNAI1 degradation , thereby suppressing breast cancer invasion and metastasis ( 49 , 53 ) .

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Expression of Dub3 blocked Snail degradation mediated by the E3 ligases Fbxl14 and Fbxw1 and beta-TRCP 1 [XREF_BIBR].
USP17L2 inhibits SNAI1.
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Dub3 mediated Snail stabilization is disrupted by a Dub3 specific inhibitor, WP1130, and Snail driven metastasis is inhibited in breast cancer.
USP17L2 affects AMOT
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USP17L2 activates AMOT.
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USP17L2 activates AMOT. 2 / 2
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We therefore considered the possibility that DUB3 might directly regulate the turnover of AMOT and LATS proteins.

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Thus DUB3 activity can promote the stability of LATS1/2 and AMOT, which act to reduce YAP activity and increase YAP turnover, while also increasing expression of ITCH, which can promote YAP turnover.
USP17L2 increases the amount of AMOT.
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Modified USP17L2 increases the amount of AMOT. 1 / 1
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Interestingly, DUB3 expression increased the levels of AMOT, AMOTL1, LATS1 and LATS2 and a decrease in YAP level.
NCOA1 affects USP17L2
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NCOA1 activates USP17L2.
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NCOA1 activates USP17L2. 2 / 2
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In support to this possibility, expression of the individual NCoA1 splice variants (NCoA and SRC1A or NCoA and SRC1E) in mESCs, both led to an increase of endogenous Dub3 mRNA without affecting Esrrb gene expression (XREF_SUPPLEMENTARY).

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In addition we present evidence that NCoA1 splice variants directly interact with Esrrb and potentiate Dub3 promoter activity.
NCOA1 increases the amount of USP17L2.
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NCOA1 increases the amount of USP17L2. 1 / 1
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In contrast, NCoA2 and NCoA3 inversely correlated with Dub3 expression, suggesting that NCoA1 may contribute to the strong cell cycle dependent oscillation of Dub3 expression levels.
USP17L2 affects CDH1
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USP17L2 decreases the amount of CDH1.
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USP17L2 decreases the amount of CDH1. 1 / 1
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Since DUB3 deubiquitinates and stabilizes SNAIL1 and consequently decreases E-cadherin expression, we hypothesized that DUB3 is critical for breast cancer cell migration and invasion in vitro.
Modified USP17L2 decreases the amount of CDH1. 1 / 1
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Expression of Dub3 in these two cell lines dramatically increased the levels of Slug and Twist and reduced E-cadherin and ER expression.
USP17L2 activates CDH1.
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USP17L2 activates CDH1. 1 / 1
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Dub3 expression induced Snail1 stabilization as well as downregulation of E-cadherin and oestrogen receptor alpha (ERalpha) in these cells (XREF_FIG).
Cytokine affects USP17L2
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Moreover , USP17 can be induced by cytokines such as interleukin ( IL ) -4 and IL-6 ( 28 ) .

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USP17 , a novel DUB , contains hyaluronan and RNA binding motifs and can be induced by cytokines such as interleukin-4 ( IL-4 ) and IL-6 ( 18 ) .
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DUB3 inhibits cell growth through regulating Hippo pathway activity.

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DUB3 inhibits cell growth through regulating Hippo pathway activity.
USP17L2 affects USP17L2
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JQ1-induced upregulation of BRD4 protein was almost completely abolished by DUB3 knockdown or inhibition of DUB3 by the CDK4/6 inhibitor PD0332991 ( Figures 7 B and 7C).

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We demonstrated that JQ1-induced upregulation of BRD4 protein was almost completely abolished by DUB3 knockdown or inhibition of DUB3 by CDK4/6 inhibitor PD0332991 ( xref ).
SCPEP1 affects USP17L2
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In breast cancer , miR-542-5p stimulated the formation of RISC to decrease the levels of DUB3 .

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Hence , we hypothesized miR-542-5p might directly modulate AGO2 into RISC , subsequently the RISC leads to repression of DUB3 , resulting in the proliferation , migration , and cell cycle were all inhibited by pristimerin .
AMOT affects USP17L2
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AMOT activates USP17L2. 2 / 2
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In light of this, we asked if AMOT and the related AMOTL1 and AMOTL2 proteins are required to mediate the effect of DUB3 on LATS kinase and YAP levels.

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Similarly, any of the three AMOT proteins appears to support the activity of DUB3 on YAP activity.
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USP17L2 inhibits cell cycle.
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Similar to our observations, previous shRNA studies have also indicated that Dub3 knockdown reduces proliferation by inhibiting the G1-S phase cell cycle progression and inhibits chemotaxis [14,15,26][MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
USP17L2 activates cell cycle.
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Dub3 promotes cell cycle progression in committed cells, although its transcript level remains low in stem cells.
USP17L2 affects ITCH
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USP17L2 decreases the amount of ITCH.
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Modified USP17L2 decreases the amount of ITCH. 1 / 1
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Expression of DUB3 strongly reduced the amount of poly-ubiquitylated ITCH (XREF_FIG).
USP17L2 activates ITCH.
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USP17L2 activates ITCH. 1 / 1
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Our results suggest that DUB3 promotes ITCH stability; we therefore asked if DUB3 would affect the stability of these Hippo proteins as well.
USP17L2 affects Cyclin
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USP17L2 increases the amount of Cyclin. 1 / 1
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We found that knockdown of DUB3 decreases cyclin A levels, whereas overexpression of DUB3 strongly increases cyclin A levels.
Modified USP17L2 increases the amount of Cyclin. 1 / 1
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We found that knockdown of DUB3 decreases cyclin A levels, whereas overexpression of DUB3 strongly increases cyclin A levels.
HDAC10 affects USP17L2
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HDAC10 inhibits USP17L2.
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HDAC10 knockdown also markedly increased DUB3 protein in C4-2 cells, and similar results were obtained in another prostate cancer cell line (PC-3).
HDAC10 decreases the amount of USP17L2.
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HDAC10 decreases the amount of USP17L2. 1 / 1
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These data suggest that NCOR2 and HDAC10 work in concert in the same complex to repress expression of DUB3 in prostate cancer cells.
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Rifampicin decreases the amount of USP17L2. 1 / 1
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Paracetamol increases the amount of USP17L2. 1 / 1
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Instead, PD0332991 induces the inactivation of DUB3, destablization of SNAIL1 protein and decrease in cell migration, thereby reducing metastasis in xenograft models, both from a breast cancer patient and a TNBC cell line.

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Only a small number of DUBs strongly affected both 53BP1 and RAD51 recruitment simultaneously, including USP29, an enzyme linked to H2A de-ubiquitylation and the recently reported HR modulator DUB3.
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Cadmium atom decreases the amount of USP17L2. 1 / 1
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Butanal affects USP17L2
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Butanal increases the amount of USP17L2. 1 / 1
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Abrine affects USP17L2
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Abrine increases the amount of USP17L2. 1 / 1
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WNT5A affects USP17L2
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WNT5A activates USP17L2. 1 / 1
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VSMCs isolated from 10 patients were subjected to in vitro WNT5A treatment with or without peg-SOD , and quantitative real time polymerase chain reaction ( q-RT-PCR ) confirmed that WNT5A increases the expression of USP17 ( Figure 8C ) .
USP17L2 affects picloram
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We show that key USP17 substrates populate two pathways that drive cell cycle progression and that USP17 activity serves to promote one pathway but inhibit the other .

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Dub3 expression induced Snail1 stabilization as well as downregulation of E-cadherin and oestrogen receptor alpha (ERalpha) in these cells (XREF_FIG).

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Only a small number of DUBs strongly affected both 53BP1 and RAD51 recruitment simultaneously, including USP29, an enzyme linked to H2A de-ubiquitylation and the recently reported HR modulator DUB3.
USP17L2 affects cell
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USP17L2 activates cell. 1 / 1
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Overall , the findings of the present study demonstrate the promotion of NSCLC cell proliferation and viability by USP17 , via the activation of the PI3K / AKT pathway .
USP17L2 affects Ubiquitin
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Recent studies have revealed that ubiquitin hydrolase Dub3 can reduce Cdc25A turnover by removing ubiquitin chains from Cdc25A protein [XREF_BIBR].
USP17L2 affects TP53BP1
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Dub3 overexpression abrogates focus formation of 53BP1 and BRCA1 in response to genotoxic stress.
USP17L2 affects TAZ
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USP17L2 inhibits TAZ. 1 / 1
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Our results showed that DUB3 inhibits YAP and TAZ activity; we asked whether this inhibition would affect Hippo mediated cell growth and proliferation.
USP17L2 affects RRAGA
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USP17L2 activates RRAGA. 1 / 1
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The overexpression of DUB3 significantly deubiquitinated RagA and rescued RagA activation.
USP17L2 affects RNF152
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Our data clearly indicated that the co-expression of DUB3 significantly reversed the inhibitory effect of RNF152 on RagA activation, confirming that RNF152 inhibits RagA activation by targeting RagA f[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
USP17L2 affects RAS
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USP17L2 inhibits RAS. 1 / 1
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More recently, we have also reported that constitutive expression of DUB-3 can block cell proliferation [XREF_BIBR, XREF_BIBR] and subsequently we have demonstrated that this is due to its regulation of the ubiquitination and activity of the ' CAAX ' box protease Ras converting enzyme 1 (RCE1) [XREF_BIBR].
USP17L2 affects Protease
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More recently, we have also reported that constitutive expression of DUB-3 can block cell proliferation [XREF_BIBR, XREF_BIBR] and subsequently we have demonstrated that this is due to its regulation of the ubiquitination and activity of the ' CAAX ' box protease Ras converting enzyme 1 (RCE1) [XREF_BIBR].
USP17L2 affects PTEN
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USP17L2 activates PTEN. 1 / 1
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While Dub3 and mir21 are significantly modulated (with upregulation and downmodulation respectively) in PTEN active cell lines, their transcripts variation is far less evident than in PTEN inactive ones.
USP17L2 affects Neoplasms
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USP17 Knockdown Impairs Tumor Proliferation and Metastasis Through Targeting MMPs Because degradation of the basement membrane by MMPs is required for tumor cell migration and invasion ( 16,17 ) , we sought to determine whether MMPs were responsible for USP17-dependent growth and invasion .
USP17L2 affects MMP9
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USP17L2 activates MMP9. 1 / 1
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Interestingly , our Western blot analysis found that depletion of USP17 dramatically reduced MMP3 and MMP9 but not MMP2 expression in both NSCLC cells ( Fig. 4A and B ) .
USP17L2 affects MMP3
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USP17L2 activates MMP3. 1 / 1
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Interestingly , our Western blot analysis found that depletion of USP17 dramatically reduced MMP3 and MMP9 but not MMP2 expression in both NSCLC cells ( Fig. 4A and B ) .
USP17L2 affects MMP2
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USP17L2 activates MMP2. 1 / 1
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Interestingly , our Western blot analysis found that depletion of USP17 dramatically reduced MMP3 and MMP9 but not MMP2 expression in both NSCLC cells ( Fig. 4A and B ) .
USP17L2 affects MCL1
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USP17L2 activates MCL1. 1 / 1
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Inhibition of BMI-1 Induces Apoptosis through Downregulation of DUB3-Mediated Mcl-1 Stabilization.
USP17L2 affects LATS2
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Modified USP17L2 activates LATS2. 1 / 1
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Interestingly, DUB3 expression increased the levels of AMOT, AMOTL1, LATS1 and LATS2 and a decrease in YAP level.
USP17L2 affects LATS1
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Modified USP17L2 activates LATS1. 1 / 1
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Interestingly, DUB3 expression increased the levels of AMOT, AMOTL1, LATS1 and LATS2 and a decrease in YAP level.
USP17L2 affects GMNN
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USP17L2 decreases the amount of GMNN. 1 / 1
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Conversely, depletion of DUB3 or USP7 reduces Geminin levels, and DUB3 knockdown increases re-replication events, analogous to the effect of Geminin depletion.
USP17L2 affects FBXL14
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Second, our study indicates that Dub3 can block the activity of beta-TRCP1 and FBXL14 to stabilize Snail1.
USP17L2 affects EZH2
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USP17L2 activates EZH2. 1 / 1
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BRD4 downregulation could repress DUB3 induced EZH2 production, and MG132 reversed DUB3 decreasing mediated BRD4 downregulation.
USP17L2 affects DNER
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USP17L2 activates DNER. 1 / 1
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DUB3 Promotes BET Inhibitor Resistance and Cancer Progression by Deubiquitinating BRD4.

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In contrast, acute Dub3 overexpression produced a signature response to oncogene induction : cells accumulated in S and G2 because of replication stress, and activated a DNA damage response.
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In addition, following UV induced DNA damage in G1, Dub3 expression markedly increases in S-phase also suggesting a role in checkpoint recovery.
USP17L2 affects CDC25A
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Recent studies have revealed that ubiquitin hydrolase Dub3 can reduce Cdc25A turnover by removing ubiquitin chains from Cdc25A protein [XREF_BIBR].
USP17L2 affects BRD3
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USP17L2 activates BRD3. 1 / 1
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Accordingly, overexpression of DUB3 increased the level of ectopically expressed full-length BRD4 protein in a dose dependent manner but had no effect on BRD4DeltaCTM mutant, BRD2 or BRD3 in PC-3 cell[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
USP17L2 affects BRD2
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USP17L2 activates BRD2. 1 / 1
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Accordingly, overexpression of DUB3 increased the level of ectopically expressed full-length BRD4 protein in a dose dependent manner but had no effect on BRD4DeltaCTM mutant, BRD2 or BRD3 in PC-3 cell[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
USP17L2 affects BRCA1
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Dub3 overexpression abrogates focus formation of 53BP1 and BRCA1 in response to genotoxic stress.
USP17L2 affects AMOTL1
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Modified USP17L2 increases the amount of AMOTL1. 1 / 1
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Interestingly, DUB3 expression increased the levels of AMOT, AMOTL1, LATS1 and LATS2 and a decrease in YAP level.
MGMT affects USP17L2
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MGMT activates USP17L2. 1 / 1
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MGMT activated DUB3 stabilizes MCL1 and drives chemoresistance in ovarian cancer.
JQ1 affects USP17L2
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JQ1 activates USP17L2. 1 / 1
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Given that JQ1 induces upregulation of DUB3 at both the mRNA and protein levels in different cell types (Borbely et al., 2015) and DUB3 binds to BRD4 and promotes its deubiquitination and protein stab[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
ITCH affects USP17L2
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ITCH inhibits USP17L2. 1 / 1
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Depletion of ITCH from this complex reduces the effects of DUB3 on YAP, and this effect was stronger when NEDD4, another E3 ligase was also removed (XREF_FIG).
HDAC affects USP17L2
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HDAC decreases the amount of USP17L2. 1 / 1
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To determine which member in the class I/II HDAC subfamilies mediates the transcriptional repression of DUB3 expression, we performed an unbiased screen by knocking down all 11 class I/II HDACs indivi[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
BABAM2 affects USP17L2
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We also failed to detect any physical interaction between BRE and DUB3 or beta-TRCP, indicating that BRE overexpression mediated CDC25A deregulation is independent of beta-TRCP and DUB3.
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Air Pollutants increases the amount of USP17L2. 1 / 1
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AMOTL2 affects USP17L2
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In light of this, we asked if AMOT and the related AMOTL1 and AMOTL2 proteins are required to mediate the effect of DUB3 on LATS kinase and YAP levels.
AMOTL1 affects USP17L2
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In light of this, we asked if AMOT and the related AMOTL1 and AMOTL2 proteins are required to mediate the effect of DUB3 on LATS kinase and YAP levels.
2-hydroxypropanoic acid decreases the amount of USP17L2. 1 / 1
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