USP47 Data Analysis

HGNC Gene Name
ubiquitin specific peptidase 47
HGNC Gene Symbol
USP47
Identifiers
hgnc:20076 NCBIGene:55031 uniprot:Q96K76
Orthologs
mgi:1922246 rgd:1310411
INDRA Statements
deubiquitinations all statements
Pathway Commons
Search for USP47
Number of Papers
46 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
MOXD1 monooxygenase DBH like 1 0.262 -0.03 -0.26 6.83e-01
BDNF brain derived neurotrophic factor 0.254
INS insulin 0.217 Reactome (2)
QSER1 glutamine and serine rich 1 0.214 -0.21 -1.27 1.42e-04
KCNJ11 potassium inwardly rectifying channel subfamily J member 11 0.21
OLFML1 olfactomedin like 1 0.205
PRMT3 protein arginine methyltransferase 3 0.204 Reactome (2) 0.68 3.65 4.96e-49

Dependency GO Term Enrichment

Gene set enrichment analysis was done on the genes correlated with USP47using 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 USP47 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
USP47 deubiquitinates CDH1. 5 / 5
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As mentioned above, E-cadherin is deubiquitinated by USP47.
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Specifically, USP47 deubiquitinates and stabilizes MAPK 25, DNA polymerase beta (Polbeta) 26, E-cadherin 27, beta-catenin 28, SNAIL 29, YAP 30, beta-Trcp 31, and katanin-p60 32.

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USP47 can be recruited to AJs and suppress the ubiquitination of E-cadherin, thus inhibiting its resultant proteasomal degradation

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USP47 can be recruited to AJs and suppress the ubiquitination of E-cadherin, thus inhibiting its resultant proteasomal degradation.

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However, as mentioned above, E-cadherin can also be deubiquitinated and stabilized by USP47.
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USP47 deubiquitinates RPS2. 2 / 2
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USP47 Promotes Tumorigenesis by Negative Regulation of p53 through Deubiquitinating Ribosomal Protein S2.

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Further mechanistic studies showed that USP47 deubiquitinated RPS2, thereby inhibiting interaction between RPS2 and MDM2, and alleviated RPS2-mediated MDM2 inhibition under normal conditions, thus inhibiting P53.
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USP47 deubiquitinates CTNNB1. 2 / 2
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Additionally, DUBs USP14, USP15, USP47, and Fam/USP9X have been reported to prevent β-catenin turnover by inhibiting its Ub-proteasomal degradation

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Specifically, USP47 deubiquitinates and stabilizes MAPK 25, DNA polymerase beta (Polbeta) 26, E-cadherin 27, beta-catenin 28, SNAIL 29, YAP 30, beta-Trcp 31, and katanin-p60 32.
USP47 deubiquitinates POLB. 2 / 2
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Specifically, USP47 deubiquitinates and stabilizes MAPK 25, DNA polymerase beta (Polbeta) 26, E-cadherin 27, beta-catenin 28, SNAIL 29, YAP 30, beta-Trcp 31, and katanin-p60 32.

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USP47 leads to the deubiquitination of SNAI1. 2 / 2
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Hypoxia induces epithelial-mesenchymal transition in colorectal cancer cells through ubiquitin-specific protease 47-mediated stabilization of Snail: A potential role of Sox9

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USP47 has been shown to induce the decomposition of E-cadherin and promote the epithelial–mesenchymal transition via Snail-deubiquitination (Choi et al., 2017).
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USP47 deubiquitinates NLRP3. 2 / 2
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However, it is not clear whether USP7 and USP47 directly contribute to NLRP3 deubiquitination or regulate the process somewhere upstream of NLRP3 inflammasome action [108].
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Conversely, deubiquitination of NLRP3 by USP7 and USP47 positively regulates inflammasome activation and USP47 is significantly downregulated in dopaminergic neurons from idiopathic PD patient post-mortem brain samples [XREF_BIBR, XREF_BIBR].
USP47 deubiquitinates SNAIL. 1 / 1
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Specifically, USP47 deubiquitinates and stabilizes MAPK 25, DNA polymerase beta (Polbeta) 26, E-cadherin 27, beta-catenin 28, SNAIL 29, YAP 30, beta-Trcp 31, and katanin-p60 32.
USP47 deubiquitinates MAPK. 1 / 1
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Specifically, USP47 deubiquitinates and stabilizes MAPK 25, DNA polymerase beta (Polbeta) 26, E-cadherin 27, beta-catenin 28, SNAIL 29, YAP 30, beta-Trcp 31, and katanin-p60 32.
USP47 deubiquitinates ubiquitinated ribosomal protein S2. 1 / 1
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We show that ubiquitinated ribosomal protein S2 (RPS2) by Mouse double minute 2 homolog (MDM2) is deubiquitinated by USP47.
USP47 deubiquitinates USP47. 1 / 1
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Furthermore, USP47 deubiquitinates itself, whereas β-TrCP promotes USP47 ubiquitination through interaction with an atypical motif in USP47.
USP47 deubiquitinates POLL. 1 / 1
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DNA Pol?β?is a component of the BER complex. It is ubiquitinated by Mule and CHIP and is deubiquitinated by USP47?
Modified USP47 leads to the deubiquitination of YBX1. 1 / 1
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XREF_FIG, USP47 overexpression significantly inhibits ubiquitination of full-length YB-1 and YB-1-S3, but not that of the truncated YB-1-S2, which can not bind USP47.

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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Knockdown of USP47 expression in human osteosarcoma U-2OS and SAOS-2 cells and breast cancer T47D, BT-20, and MCF7 cells significantly induced apoptosis and improved the sensitivity to chemotherapeutic drugs.Ubiquitin-specific peptidase 47 knockdown inhibited the proliferation of A549 lung cancer cells and PC3 prostate cancer cells by deubiquitinating β-catenin (Shi et al., 2015).
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Compound 1, a selective inhibitor of USP7 and USP47 with moderate potency, demonstrates inhibition of USP7 in cells and induces elevated p53 and apoptosis in cancer cell lines.

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USP47 facilitated osteosarcoma cell invasion and migration, and suppressed apoptosis.

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Notably, selective dual inhibitors of USP7 and USP47 have been synthesized and induced accumulation of p53 and apoptosis in human cancer cell lines [XREF_BIBR].

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A class of dual small molecule inhibitors of USP7 and USP47 has been identified to promote p53 activity and apoptosis in MM and B-cell leukemia cells in vitro and xenograft models.

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USP47 facilitated osteosarcoma cell invasion and migration , and suppressed apoptosis ( 46 ) .

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USP47 knockdown attenuated myocardial cell I/R injury by inhibiting apoptosis.

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In agreement with this result, we observed that silencing of USP47 augments the apoptosis of MCF-7 breast cancer cells, which are known to be resistant to inhibition of NF-kappaB.

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In cultured CRC cells, knockdown of USP47 increased pyroptosis and apoptosis induced by chemotherapeutic doxorubicin.
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USP47 promotes apoptosis in rat myocardial cells after ischemia and reperfusion injury via NF-kappaB activation.

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USP47 has also been described as an interaction partner for the ubiquitin E3 ligase complex, b-TrCP, with the authors of this study showing that silencing of USP47 expression inhibits cell survival and sensitises cells to chemotherapeutic agent-induced apoptosis [139] .

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USP47 induced apoptosis was potently counteracted by the NF-kappaB inhibitor, and cytoplasmic NF-kappaB was increased and nuclear NF-kappaB was decreased.

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USP47 has also been described as an interaction partner for the ubiquitin E3 ligase complex, β-TrCP, with the authors of this study showing that silencing of USP47 expression inhibits cell survival and sensitises cells to chemotherapeutic agent-induced apoptosis [139].

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Downregulation of USP47 decreased apoptosis induced by ischemia/reperfusion injury, increased survivin and cytoplasmic NF-κB, and decreased cleaved caspase-3 and nuclear NF-κB. NF-κB inhibitors could effectively inhibit USP47-induced apoptosis, increase cytoplasmic NF-κB, and decrease nuclear NF-κB. Luciferase reporter genes showed that USP47 promoted NF-κB promoter activity.
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USP47-deficient MEF cells isolated from a USP47 knockout mouse model revealed that USP47 knockout significantly increased the levels of ultraviolet-induced apoptosis (Peschiaroli et al., 2010).
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USP47 activates Cell Survival.
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Silencing of USP47 inhibits cell survival and sensitizes cells to chemotherapic agent induced apoptosis.

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In the present study, USP47 was identified as a target of miR-454, and USP47 knockdown significantly inhibited cell viability and DDP resistance in NPC cells compared with the shNC group.

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It was recently demonstrated that silencing of USP47 inhibits cell survival and sensitizes cells to DNA damaging agents (Peschiaroli et al., 2010).

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Compared with the shNC group, USP47 knockdown significantly suppressed NPC cell viability and DDP resistance, which was significantly reversed by co-transfection with miR-454 inhibitor.

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USP47 has also been described as an interaction partner for the ubiquitin E3 ligase complex, beta-TrCP, with the authors of this study showing that silencing of USP47 expression inhibits cell survival and sensitises cells to chemotherapeutic agent induced apoptosis [XREF_BIBR].

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Silencing of USP47 decreases cell survival and augments the cytotoxic effects of antitumor drugs on a variety of tumor cells, including osteosarcoma and breast cancer cell lines.

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Compared with the shNC group , USP47 knockdown significantly suppressed NPC cell viability and DDP resistance , which was significantly reversed by co-transfection with miR-454 inhibitor .

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The CCK-8 assay results demonstrated that USP47 knockdown significantly reduced cell viability compared with the shNC group, which was significantly reversed by co-transfection with miR-454 knockdown in 5-8F/DDP and SUNE-1 and DDP cells (XREF_FIG).

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Additionally, the utilization of AZD6738 (50nM), an ATR pathway inhibitor, partially inhibits USP47 knockdown induced suppression of cell viability in CML cells.

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The CCK-8 assay results demonstrated that USP47 knockdown significantly reduced cell viability compared with the shNC group , which was significantly reversed by co-transfection with miR-454 knockdown in 5-8F / DDP and SUNE-1 / DDP cells ( Fig. 6C ) .
USP47 inhibits Cell Survival.
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Notably, genetic or siRNA mediated depletion of USP47 induced accumulation of Cdc25A, decreased cell survival and augmented the cytotoxic effects of anticancer drugs.

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Notably, genetic or siRNA mediated depletion of USP47 decreases cell survival and augments the anti-proliferative effect of anticancer drugs, providing a novel potential target for anticancer therapies.

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Finally , we show that depletion of USP47 induces p53 and therefore inhibits cell proliferation , colony formation , and tumor progression in cancer cell lines and a mouse xenograft model .

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Functional analysis shows that USP47 knockdown represses proliferation of CML cells sensitive or resistant to imatinib in vitro and in vivo.

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For example, USP47 overexpression accelerated ovarian cancer cell development, whereas USP47 knockdown inhibited gastric cancer cell proliferation.

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USP47 knockdown inhibits proliferation of CML cells.

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USP47 silencing reduces proliferation and migration of colorectal cancer cells and suppresses the self-renewal of CCSCs by downregulating the expression of cancer stem cell markers, including CD44, CD133, CD166, OCT4 and NANOG.

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Silencing Usp47 inhibits BCR-ABL T315I -induced CML and proliferation of KBM T315I in a xenograft mouse model.

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Specifically, we demonstrate that USP47 is highly expressed in primary CML cells and promotes cell proliferation, while Usp47 knockout significantly prolongs the survival of BCR-ABL and BCR-ABL T315I -induced CML mice by reducing leukemia stem and progenitor cells.

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USP47 functions as a DUB for YAP in colorectal cancer, USP47 elevation leads to stabilization of YAP and promotes colorectal cancer cell proliferation XREF_BIBR.

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Moreover, USP47 knockdown could repress CRC cell proliferation, which could be rescued by YAP overexpression (Pan et al., 2020).
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The deficiency of USP47 impaired the transcriptional activity of SATB1 target genes and inhibited cell proliferation, migration, and tumorigenesis in a mouse model of colon cancer.
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Downregulation of USP47 inhibited the proliferation of imatinib-sensitive or drug-resistant CML cells.
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USP47 deficiency impairs transcriptional activity of SATB1 target genes and inhibits colon cancer cell proliferation, migration, and tumorigenesis in a mouse model of colon cancer.

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Here we report that upregulation of USP47 under hypoxic conditions stimulates EMT in CRC cells and subsequently their metastatic potential.

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However, the relationship between EMT mediated by USP47 and E-cadherin was not explored in this study.
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Silencing of USP47 accelerated the proteasomal degradation of Snail and inhibited EMT.

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By utilizing the microarray database system of the Cancer Genome Atlas, we identified ubiquitin specific protease 47 (USP47), a deubiquitinating enzyme, as a potential mediator of hypoxia induced EMT.

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Ubiquitin-specific peptidase 47 also helps to promote EMT in normal cells (Silvestrini et al., 2020).
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The enhancement of USP47 in colorectal cancer cells under hypoxic conditions induced the disassembly of E-cadherin and promoted EMT through deubiquitination of Snail.

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These results suggested that USP47 could mediate EMT by stabilizing SATB1 (Yu et al., 2019).
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Because hypoxia induced USP47 expression enhanced EMT by stabilizing Snail, we investigated the contribution of USP47 to tumor growth and invasion in vivo.

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Additionally, chemical inhibition of USP47 reduced the expressions of several EMT markers, including CDH1, CTNNB1, and SNAIL, and reversed the morphological changes in MCF-10A cells undergoing EMT (Silvestrini et al., 2020).
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USP47 increases the amount of epithelial to mesenchymal transition.
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In line with the in vitro findings, knockdown of USP47 abrogated the expression of EMT markers in transplanted tumors, and this led to suppression of progression and invasiveness of CRC cells.

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After validating USP47 alterations using MRM and antibody based assays, we demonstrated that the chemical inhibition of USP47 with the inhibitor P5091 reduced expression of EMT markers and reverted morphological changes in MCF-10A cells undergoing EMT.

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Silencing of USP47 promotes EMT in CRC cells under hypoxic conditions.
USP47 affects DNA Damage
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USP47 activates DNA Damage.
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Mechanistic studies have shown that stable Y-box binding protein 1 (YB-1) contributed to USP47-mediated DNA damage repair in CML cells.
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USP47 overexpression in YB-1 and/or Polbeta depletion cells can not abrogate gammaH 2 AX expression, indicating that YB-1 contributes more to USP47 mediated DNA damage repair than Polbeta in CML cells.

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YB-1 contributes to USP47 mediated DNA damage repair in CML cells.

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The results indicate that YB-1 is involved in USP47 mediated DNA damage repair in CML cells.

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Taken together, these data demonstrate that by controlling stability of the cytoplasmic form of Pol beta, USP47 modulates the efficiency of DNA damage repair by the BER pathway and maintains genome in[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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We further demonstrated that YB-1, a novel substrate of USP47, contributes to USP47 mediated DNA damage repair.

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As a substrate of USP47, YB-1 contributes to USP47 mediated DNA damage repair in CML cells.

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To assess the contribution of YB-1 and Polbeta to USP47 mediated DNA damage repair in CML cells, we overexpressed USP47 in YB-1 and/or POLB knockdown K562 and KBM5 T315I cells.

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Mechanistic studies show that stabilizing Y-box binding protein 1 contributes to USP47 mediated DNA damage repair in CML cells.
USP47 inhibits DNA Damage.
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As DNA damage repair plays an essential role in the maintenance or generation of CML stem and progenitor cells XREF_BIBR, XREF_BIBR, we hypothesized that DNA damage induced by USP47 knockdown might be vital to CML stem and progenitor cells.

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Phenolic compounds not only inhibited the 26S activity but also decreased the USP47 levels, which reduce the DNA damage repair rate during oxidative stress; in addition, the presence of DNA fragments, procaspase-3 and a decreased poly (ADP-ribose) polymerase also appeared as a result of the above conditions.
USP47 affects CDH1
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USP47 activates CDH1.
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USP47 activates CDH1. 5 / 5
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The enhancement of USP47 in colorectal cancer cells under hypoxic conditions induced the disassembly of E-cadherin and promoted EMT through deubiquitination of Snail.

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Depletion of KIFC3 or USP47 promotes cleavage of E-cadherin at a juxtamembrane region of the cytoplasmic domain, resulting in the production of a 90-kDa fragment and the internalization of E-cadherin.

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Therefore, the modulation of E-cadherin by USP47 may be related to the cell states.
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KIFC3 and USP47 depletion enhances formation of a unique E-cadherin fragment.

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Additionally, chemical inhibition of USP47 reduced the expressions of several EMT markers, including CDH1, CTNNB1, and SNAIL, and reversed the morphological changes in MCF-10A cells undergoing EMT (Silvestrini et al., 2020).
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USP47 decreases the amount of CDH1.
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USP47 decreases the amount of CDH1. 2 / 2
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Besides, USP47 knockout could increase E-cadherin expression and inhibited β-catenin expression in HCT116 cells, which is the reverse process of EMT.
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Knockdown of USP47 suppressed the expression of vimentin and N-cadherin and restored E-cadherin expression under hypoxic conditions.
USP47 bound to SNAI1 decreases the amount of CDH1. 1 / 1
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In a normal state, USP47 binds to E-cadherin, preventing its degradation; however, when cells are under hypoxic conditions or during EMT, the binding of USP47 to Snail and SATB1 is enhanced, thereby inhibiting the expression of E-cadherin.
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USP47 bound to SATB1 decreases the amount of CDH1. 1 / 1
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In a normal state, USP47 binds to E-cadherin, preventing its degradation; however, when cells are under hypoxic conditions or during EMT, the binding of USP47 to Snail and SATB1 is enhanced, thereby inhibiting the expression of E-cadherin.
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USP47 increases the amount of CDH1.
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USP47 increases the amount of CDH1. 1 / 1
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Knockdown of USP47 suppressed the expression of vimentin and N-cadherin and restored E-cadherin expression under hypoxic conditions.
USP47 affects CDC25A
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USP47 activates CDC25A.
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USP47 activates CDC25A. 4 / 4
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Moreover, we found that in response to hydroxyurea, Cdc25A was degraded in USP47 depleted cells to similar levels as in control cells (XREF_FIG), implying a transcriptional regulation of Cdc25A induced by USP47 depletion.

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Notably, genetic or siRNA mediated depletion of USP47 induced accumulation of Cdc25A, decreased cell survival and augmented the cytotoxic effects of anticancer drugs.

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Moreover, USP47 depletion induced upregulation of Cdc25A to similar levels as the silencing of betaTrcp (XREF_SUPPLEMENTARY).

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Depletion of USP47 induced accumulation of Cdc25A and decreased cell survival [XREF_BIBR].
USP47 increases the amount of CDC25A.
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USP47 increases the amount of CDC25A. 3 / 3
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Although we have not elucidated yet the precise mechanism through which USP47 depletion causes Cdc25A upregulation, our results suggest that USP47 could potentially regulate Cdc25A expression at a transcriptional level.

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To verify this, we performed a quantitative real-time PCR and we found that USP47 but not beta-Trcp depletion increases Cdc25A mRNA levels (XREF_FIG).

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Collectively, these results showed that USP47 potentially regulates Cdc25A expression at mRNA level, suggesting that USP47 does not regulate beta-Trcp activity.
USP47 decreases the amount of CDC25A.
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USP47 decreases the amount of CDC25A. 1 / 1
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Silencing of USP47 increases Cdc25A protein levels.
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Valproic acid decreases the amount of USP47. 7 / 7
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USP47 affects TP53
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USP47 inhibits TP53.
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USP47 inhibits TP53. 4 / 4
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Notably, selective dual inhibitors of USP7 and USP47 have been synthesized and induced accumulation of p53 and apoptosis in human cancer cell lines [XREF_BIBR].

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Compound 1, a selective inhibitor of USP7 and USP47 with moderate potency, demonstrates inhibition of USP7 in cells and induces elevated p53 and apoptosis in cancer cell lines.

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A class of dual small molecule inhibitors of USP7 and USP47 has been identified to promote p53 activity and apoptosis in MM and B-cell leukemia cells in vitro and xenograft models.

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Finally , we show that depletion of USP47 induces p53 and therefore inhibits cell proliferation , colony formation , and tumor progression in cancer cell lines and a mouse xenograft model .
USP47 increases the amount of TP53.
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USP47 increases the amount of TP53. 1 / 1
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USP47 knockdown led to an increased binding of RPS2 to MDM2, inhibiting MDM2 activity and upregulating p53 levels under ribosomal stress, thereby inhibiting cell proliferation, colony formation, and tumor progression (Cho et al., 2020).
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USP47 decreases the amount of TP53.
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USP47 decreases the amount of TP53. 1 / 1
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USP47 knockdown led to an increased binding of RPS2 to MDM2, inhibiting MDM2 activity and upregulating p53 levels under ribosomal stress, thereby inhibiting cell proliferation, colony formation, and tumor progression (Cho et al., 2020).
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USP47 affects SNAI1
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USP47 activates SNAI1.
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USP47 activates SNAI1. 3 / 3
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Because hypoxia induced USP47 expression enhanced EMT by stabilizing Snail, we investigated the contribution of USP47 to tumor growth and invasion in vivo.

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Silencing of USP47 accelerated the proteasomal degradation of Snail and inhibited EMT.

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Additionally, chemical inhibition of USP47 reduced the expressions of several EMT markers, including CDH1, CTNNB1, and SNAIL, and reversed the morphological changes in MCF-10A cells undergoing EMT (Silvestrini et al., 2020).
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USP47 increases the amount of SNAI1.
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USP47 increases the amount of SNAI1. 2 / 2
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We found that the USP47 elevated the protein level of Snail without influencing the expression of its mRNA.

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Transient knockdown of USP47 in DLD-1 cells lowered the expression of Snail protein.
USP47 inhibits SNAI1.
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USP47 inhibits ubiquitinated SNAI1. 1 / 1
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Silencing of USP47 significantly increased the accumulation of ubiquitinated Snail.
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USP47 maintains the stemness of colorectal cancer cells and is inhibited by parthenolide.

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USP47 maintains the stemness of colorectal cancer cells and is inhibited by parthenolide .

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USP47 maintains the stemness of colorectal cancer cells and is inhibited by parthenolide.
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USP47 maintains the stemness of colorectal cancer cells and is inhibited by parthenolide.
SOX9 affects USP47
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SOX9 increases the amount of USP47.
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SOX9 increases the amount of USP47. 3 / 3
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Furthermore, the silencing of Sox9 suppressed the expression of USP47 protein and manifestation of EMT.

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Sox9 then migrates to the nucleus and upregulates the expression of USP47, which hampers the ubiquitination of Snail, thereby preventing the proteasomal degradation of Snail.

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Sox9 induces expression of USP47 by binding to its promoter region under hypoxic conditions.
SOX9 activates USP47.
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SOX9 activates USP47. 1 / 1
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Notably, hypoxia induced USP47 upregulation was mediated by Sox9.
E2F7 affects USP47
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E2F7 activates USP47.
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E2F7 activates USP47. 3 / 3
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E2F7 upregulated USP47 expression by downregulating miR-199b in SW403 cells .

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USP47 upregulation by E2F7 deubiquitin-modifies MAPK K48 ubiquitin chain to stabilize MAPK .

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Therefore, we are convinced that present results show that E2F7 suppressed the miR-199b expression and promoted USP47 to stabilize MAPK proteins, thereby contributing to colon cancer development.
E2F7 increases the amount of USP47.
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E2F7 increases the amount of USP47. 1 / 1
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E2F7 upregulated USP47 expression by downregulating miR-199b in SW403 cells.
USP47 affects MAPK
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USP47 decreases the amount of MAPK.
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USP47 decreases the amount of MAPK. 2 / 2
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Like many of the candidates identified in our initial genome-wide screen, Usp47 RNAi was found to cause a decrease in MAPK protein levels (XREF_FIG) [XREF_BIBR], whereas it did not visibly alter the expression levels of JNK (FBgn0000229) and p38b (FBgn0024846), two other members of the MAPK family, nor of other RAS-MAPK pathway proteins (XREF_FIG).

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However, as Usp47 RNAi only partially depletes MAPK levels compared to the effect of mapk dsRNA itself (XREF_FIG), it might be expected that another DUB is acting redundantly to protect MAPK from complete degradation, in which case this factor should display an aggravating genetic interaction with Usp47 RNAi (XREF_SUPPLEMENTARY).
USP47 inhibits MAPK.
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USP47 inhibits MAPK. 1 / 1
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We found labeled MAPK to be degraded more rapidly in cells treated with Usp47 RNAi (XREF_FIG).
USP47 activates MAPK.
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USP47 activates MAPK. 1 / 1
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Moreover, this event appears to be specific to MAPK, as no other core components of the pathway nor other Drosophila MAPK like proteins, JNK (bsk; FBgn0000229) and p38B (FBgn0015765), are modulated by USP47 function.
Bisphenol A affects USP47
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Bisphenol A increases the amount of USP47. 3 / 3
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USP47 affects Wnt
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USP47 activates Wnt. 2 / 3
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The results indicate that USP47 induces a positive process in Wnt and beta-catenin signaling while increasing the stability of beta-catenin [XREF_BIBR, XREF_BIBR].

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USP47 also augments Wnt signaling through deubiquitination of beta-catenin in A549 lung and PC3 prostate cancer cells 18.
USP47 affects NLRP3
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USP47 activates NLRP3. 3 / 3
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Moreover, USP7, USP47, and BRCC3 and ABRO can activate the NLRP3 inflammasome.

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Inhibition of USP7 and USP47 impairs NLRP3 inflammasome activation in macrophages.

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It is then possible that this process is regulated by K11 linked ubiquitin chains, yet it is also possible that USP7 and USP47 do not directly target NLRP3 and that an additional regulated protein, upstream of this process, is mediating this effect.
USP47 affects SATB1
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USP47 activates SATB1.
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USP47 activates SATB1. 2 / 2
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The deficiency of USP47 impaired the transcriptional activity of SATB1 target genes and inhibited cell proliferation, migration, and tumorigenesis in a mouse model of colon cancer.
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These results suggested that USP47 could mediate EMT by stabilizing SATB1 (Yu et al., 2019).
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USP47 inhibits SATB1.
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USP47 inhibits SATB1. 1 / 1
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USP47 deficiency impairs transcriptional activity of SATB1 target genes and inhibits colon cancer cell proliferation, migration, and tumorigenesis in a mouse model of colon cancer.
USP47 affects CTNNB1
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USP47 activates CTNNB1.
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USP47 activates CTNNB1. 2 / 2
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The results indicate that USP47 induces a positive process in Wnt and beta-catenin signaling while increasing the stability of beta-catenin [XREF_BIBR, XREF_BIBR].

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Additionally, chemical inhibition of USP47 reduced the expressions of several EMT markers, including CDH1, CTNNB1, and SNAIL, and reversed the morphological changes in MCF-10A cells undergoing EMT (Silvestrini et al., 2020).
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USP47 decreases the amount of CTNNB1.
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USP47 decreases the amount of CTNNB1. 1 / 1
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Besides, USP47 knockout could increase E-cadherin expression and inhibited β-catenin expression in HCT116 cells, which is the reverse process of EMT.
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SLC4A1 affects USP47
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SLC4A1 inhibits USP47.
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SLC4A1 inhibits USP47. 2 / 2
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In this study , we could show that DIs , especially those inhibiting USP7 and USP47 , enhance the entry of Gag into the UPS and thus into the MHC-I pathway , indicating that specific DUBs play an important role in the regulation of Gag ubiquitination .

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Cells were treated with the following DIs: P22077, which specifically inhibits the DUBs USP7 and USP47 [59], the DI P5091, which only inhibits USP7 [60], and the DI PR-619, that, in addition to USP7 and USP47, inhibits the DUBs Josephin domain containing 2 (JOSD2), deneddylase 1 (DEN1), UCH-L3, UCH-L5, USP2, 4, 5, 8, 15, 20, and 28 [59].
SLC4A1 activates USP47.
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SLC4A1 activates USP47. 1 / 1
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Cells were treated with the following DIs: P22077, which specifically inhibits the DUBs USP7 and USP47 [59], the DI P5091, which only inhibits USP7 [60], and the DI PR-619, that, in addition to USP7 and USP47, inhibits the DUBs Josephin domain containing 2 (JOSD2), deneddylase 1 (DEN1), UCH-L3, UCH-L5, USP2, 4, 5, 8, 15, 20, and 28 [59].
Nigericin affects USP47
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Nigericin inhibits USP47.
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At the concentration used in this experiment, we observed that P22077 did not cause a complete inhibition of the nigericin induced increase in activity of USP7 and USP47 that may be due to the irreversible action of the ABP versus the reversible inhibitor 24.
Nigericin increases the amount of USP47.
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Nigericin increases the amount of USP47. 1 / 1
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Although LPS treatment did not induce any differences in either protein level and activity of USP47, nigericin increased both the USP47 level and activity, and an unknown post-translational modification of USP47 may contribute to the modulation induced by nigericin (Palazón-Riquelme et al., 2018).
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Nigericin activates USP47.
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Nigericin‐induced activation of both USP7 and USP47 was not dependent on LPS priming (Fig xref A, final lane).
Phenylmercury acetate decreases the amount of USP47. 2 / 2
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Nickel atom affects USP47
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Nickel atom decreases the amount of USP47. 2 / 2
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Fbxw1 affects USP47
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Fbxw1 activates USP47. 2 / 2
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Depletion of beta-Trcp by siRNA did not induce stabilization of USP47 (XREF_FIG).

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However, we can not rule out the possibility that beta-Trcp might target USP47 for proteasome dependent degradation in response to a stimulus that we did not analyze.
Entinostat affects USP47
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Entinostat decreases the amount of USP47. 2 / 2
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Cyclosporin A increases the amount of USP47. 2 / 2
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Benzo[a]pyrene decreases the amount of USP47. 2 / 2
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USP7 affects USP47
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USP7 inhibits USP47. 2 / 2
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Due to the multifaceted roles of USP7, many inhibitors have been developed targeting USP7, such as P022077, HBX 41,108, HBX-19,818, HBX-28,258, P5091, Cpd 14 and P22077, in which the latter two molecules also inhibit USP47 [XREF_BIBR - XREF_BIBR].

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Due to the multifaceted roles of USP7, many inhibitors have been developed targeting USP7, such as P022077, HBX 41,108, HBX-19,818, HBX-28,258, P5091, Cpd 14 and P22077, in which the latter two molecules also inhibit USP47.
USP47 affects math-33
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USP47 activates math-33. 2 / 2
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Furthermore, depletion of these 22 DUBs in math-33 (tm3561) mutants revealed that depletion of T05H10.1, hereafter referred to as USP-47, caused synthetic lethality in the math-33 (tm3561) mutant by increasing embryonic lethality from 35% to 95% (XREF_FIG), and by increasing the lethality of a second probable null math-33 allele, ok2974, from 45% to 93%.

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We tested whether the major action of MATH-33 and USP-47 was to antagonize poly-ubiquitylation by asking whether compromising protein turnover could suppress the lethality and polarity defects of math-33 (tm3561); usp-47 (RNAi) worms.
USP47 affects cell death
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As shown in XREF_FIG, the genetic depletion of USP47 in mouse embryonic fibroblasts increased the sensitivity to the ultraviolet induced cell death.

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The pro apoptotic effect elicited by the silencing of USP47 prompted us to analyze whether depletion of USP47 could increase cell death triggered by anticancer drugs in different tumor cell lines.
USP47 affects YBX1
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USP47 activates YBX1. 2 / 2
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In contrast, USP47 knockdown or P22077 treatment reduces the half-life of YB-1.

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We then investigated whether USP47 influences the stability of YB-1 and found that transient transfection of USP47 prolonged the half-life of YB-1 in K562 cells.
USP47 affects TIMM8A
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USP47 activates TIMM8A. 2 / 2
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In the present study, USP47 was identified as a target of miR-454, and USP47 knockdown significantly inhibited cell viability and DDP resistance in NPC cells compared with the shNC group.

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Compared with the shNC group, USP47 knockdown significantly suppressed NPC cell viability and DDP resistance, which was significantly reversed by co-transfection with miR-454 inhibitor.
USP47 affects Neoplasms
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Ubiquitin-specific peptidase 47 expression is elevated in many tumors and is involved in multiple expression regulating mechanisms, including transcriptional, post-transcriptional, and post-translational modifications.
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Overexpression of USP47 could reduce the tumor inhibition induced by LINC00668 knockout (Hu et al., 2019).
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Overexpression of USP47 enhances invasiveness and metastatic potential of CRC cells.

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In addition, the USP47 knockdown attenuated the invasiveness of DLD-1 cells.
MIR454 affects USP47
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MIR454 activates USP47. 2 / 2
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Compared with the shNC group , KCNQ1OT1 knockdown significantly downregulated USP47 expression , and miR-454 knockdown significantly reversed shKCNQ1OT1-mediated effects on USP47 expression .

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KCNQ1OT1 confers DDP resistance in NPC cells via upregulating USP47 expression by sponging miR-454 Subsequently , the RT-qPCR results demonstrated that miR-454 and USP47 expression levels were significantly decreased in 5-8F / DDP and SUNE-1 / DDP cells following transfection with miR-454 inhibitor or shUSP47 compared with the NC inhibitor and shNC groups , respectively , which suggested that miR-454 inhibitor and shUSP47 downregulated miR-454 and USP47 expression levels in DDP-resistant NPC cells , respectively ( Fig. 6A and B ) .
MIR199B affects USP47
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E2F7 Transcriptionally Inhibits MicroRNA-199b Expression to Promote USP47 , Thereby Enhancing Colon Cancer Tumor Stem Cell Activity and Promoting the Occurrence of Colon Cancer microRNAs ( miRNAs ) can modulate the expression level of genes in a post-transcription manner , which are closely related to growth and metastasis of colon cancer .

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E2F7 Transcriptionally Inhibits MicroRNA-199b Expression to Promote USP47 , Thereby Enhancing Colon Cancer Tumor Stem Cell Activity and Promoting the Occurrence of Colon Cancer .
KCNQ1OT1 affects USP47
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Furthermore , compared with the shNC group , KCNQ1OT1 knockdown significantly downregulated USP47 expression , which was significantly counteracted by miR-454 knockdown .

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Compared with the shNC group , KCNQ1OT1 knockdown significantly downregulated USP47 expression , and miR-454 knockdown significantly reversed shKCNQ1OT1-mediated effects on USP47 expression .
4,4'-diaminodiphenylmethane decreases the amount of USP47. 2 / 2
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USP47 affects cell growth
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USP47 inhibits cell growth.
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Silencing of USP47 induced a cell growth defect that appeared on day 6 and was sustained through day 9 (XREF_FIG), indicating that depletion of USP47 inhibits cell growth, likely by inducing apoptosis.
USP47 activates cell growth.
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Silencing of USP47 induced a cell growth defect that appeared on day 6 and was sustained through day 9 (XREF_FIG), indicating that depletion of USP47 inhibits cell growth, likely by inducing apoptosis.
USP47 affects amoxicillin
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USP47 decreases the amount of amoxicillin. 1 / 1
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Furthermore, Usp47 knockout significantly enhances the expression of gammaH 2 AX in GFP + BM cells from BCR-ABL T315I -induced CML mice.
Modified USP47 decreases the amount of amoxicillin. 1 / 1
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USP47 overexpression in YB-1 and/or Polbeta depletion cells can not abrogate gammaH 2 AX expression, indicating that YB-1 contributes more to USP47 mediated DNA damage repair than Polbeta in CML cells.
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USP47 inhibits Carcinogenesis.
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The deficiency of USP47 impaired the transcriptional activity of SATB1 target genes and inhibited cell proliferation, migration, and tumorigenesis in a mouse model of colon cancer.
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USP47 activates Carcinogenesis.
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USP47 Promotes Tumorigenesis by Negative Regulation of p53 through Deubiquitinating Ribosomal Protein S2 .
USP47 affects BCR
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USP47 inhibits BCR.
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USP47 inhibits BCR. 1 / 1
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Downregulation of USP47 inhibited the proliferation of imatinib-sensitive or drug-resistant CML cells.
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USP47 activates BCR.
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USP47 activates BCR. 1 / 1
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USP47 knockout significantly inhibited BCR-ABL and BCR-ABL -induced mouse CML with reduced of LIN Sca1 c-kit CML stem cells/progenitor cells.
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Moreover, in a search for additional factors that act similarly to the newly identified E2/E3 enzymes, we found that KCMF1 (FBgn0037655), a zinc finger containing protein that physically interacts with POE, also antagonized USP47 activity.
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Trichostatin A decreases the amount of USP47. 1 / 1
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Titanium dioxide decreases the amount of USP47. 1 / 1
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Tetrachloromethane decreases the amount of USP47. 1 / 1
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Succimer affects USP47
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Succimer increases the amount of USP47. 1 / 1
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Sodium arsenate increases the amount of USP47. 1 / 1
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Selenium atom decreases the amount of USP47. 1 / 1
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Resveratrol affects USP47
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Resveratrol decreases the amount of USP47. 1 / 1
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Pentachlorophenol increases the amount of USP47. 1 / 1
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Nefazodone affects USP47
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Nefazodone increases the amount of USP47. 1 / 1
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Methylmercury chloride decreases the amount of USP47. 1 / 1
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Methamphetamine decreases the amount of USP47. 1 / 1
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Magnetite nanoparticle increases the amount of USP47. 1 / 1
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Jinfukang affects USP47
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Jinfukang decreases the amount of USP47. 1 / 1
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Imidazolide affects USP47
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Imidazolide decreases the amount of USP47. 1 / 1
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In contrast, BCR-ABL knockdown or IM treatment attenuates the expression of USP47 at the mRNA and protein levels.
Imatinib affects USP47
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Imatinib decreases the amount of USP47. 1 / 1
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And imatinib (IM) treatment attenuated the expression of USP47.
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Hsa-miR-98-5p decreases the amount of USP47. 1 / 1
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Hsa-miR-8066 decreases the amount of USP47. 1 / 1
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Hsa-miR-7112-3p decreases the amount of USP47. 1 / 1
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Hsa-miR-4711-5p decreases the amount of USP47. 1 / 1
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Hsa-miR-4500 decreases the amount of USP47. 1 / 1
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Hsa-miR-4458 decreases the amount of USP47. 1 / 1
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Hsa-miR-34a-5p decreases the amount of USP47. 1 / 1
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Hsa-miR-218-5p decreases the amount of USP47. 1 / 1
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Hsa-miR-21-5p decreases the amount of USP47. 1 / 1
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Hsa-miR-204-5p decreases the amount of USP47. 1 / 1
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Hsa-miR-202-3p decreases the amount of USP47. 1 / 1
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Hsa-miR-124-3p decreases the amount of USP47. 1 / 1
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Hsa-let-7i-5p decreases the amount of USP47. 1 / 1
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Hsa-let-7g-5p decreases the amount of USP47. 1 / 1
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Hsa-let-7f-5p decreases the amount of USP47. 1 / 1
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Hsa-let-7e-5p decreases the amount of USP47. 1 / 1
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Hsa-let-7d-5p decreases the amount of USP47. 1 / 1
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Hsa-let-7c-5p decreases the amount of USP47. 1 / 1
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Hsa-let-7b-5p decreases the amount of USP47. 1 / 1
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Hsa-let-7a-5p decreases the amount of USP47. 1 / 1
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Hexabromocyclododecane decreases the amount of USP47. 1 / 1
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Flutamide affects USP47
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Flutamide increases the amount of USP47. 1 / 1
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Endosulfan affects USP47
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Endosulfan decreases the amount of USP47. 1 / 1
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Doxorubicin affects USP47
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Doxorubicin increases the amount of USP47. 1 / 1
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Dorsomorphin decreases the amount of USP47. 1 / 1
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Disodium selenite increases the amount of USP47. 1 / 1
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Dicrotophos affects USP47
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Dicrotophos decreases the amount of USP47. 1 / 1
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Dibutyl phthalate increases the amount of USP47. 1 / 1
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Copper(II) sulfate increases the amount of USP47. 1 / 1
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Cobalt dichloride increases the amount of USP47. 1 / 1
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Cisplatin affects USP47
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Cisplatin decreases the amount of USP47. 1 / 1
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