USP51 Data Analysis

HGNC Gene Name
ubiquitin specific peptidase 51
HGNC Gene Symbol
USP51
Identifiers
hgnc:23086 NCBIGene:158880 uniprot:Q70EK9
Orthologs
mgi:3588217 rgd:1562211
INDRA Statements
deubiquitinations all statements
Pathway Commons
Search for USP51
Number of Papers
16 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
SLC9A7 solute carrier family 9 member A7 0.23 0.01 -0.05 9.57e-01
PAGE4 PAGE family member 4 0.225
WNK3 WNK lysine deficient protein kinase 3 0.224
GPR173 G protein-coupled receptor 173 0.219
TIMP1 TIMP metallopeptidase inhibitor 1 0.217 0.06 0.24 5.54e-01
SLCO1B7 solute carrier organic anion transporter family member 1B7 (putative) 0.212
MAGEH1 MAGE family member H1 0.212

Dependency GO Term Enrichment

Gene set enrichment analysis was done on the genes correlated with USP51using the terms from Gene Ontology and gene sets derived from the Gene Ontology Annotations database via MSigDB.

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

GO Identifier GO Name GO Type p-value p-value (adj.) q-value
GO:0099587 inorganic ion import across plasma membrane Biological Process 2.87e-04 4.68e-02 9.55e-03

Literature Mining

INDRA was used to automatically assemble known mechanisms related to USP51 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
USP51 leads to the deubiquitination of ZEB1. 3 / 3
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ubibrowser
By screening a human deubiquitinase library, we identified USP51 as a deubiquitinase that binds, deubiquitinates, and stabilizes ZEB1.

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Lastly, knockdown of USP51 promoted ZEB1 ubiquitination, leading to ZEB1 degradation.

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USP51 promotes deubiquitination and stabilization of ZEB1.
USP51 deubiquitinates Histone_H2B. 2 / 2
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The requirement of ATXN7L3 for H2B deubiquitination by USP22, USP27x, and USP51 suggests that all three use the ATXN7L3 zinc finger to dock the H2A and H2B acidic patch in a manner similar to that shown in the structure of the yeast DUB module bound to ubiquitinated nucleosomes.

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The requirement of ATXN7L3 for H2B deubiquitination by USP22, USP27x, and USP51 suggests that the ATXN7L3 zinc finger plays a role analogous to that of the Sgf11 zinc finger in docking human SAGA DUB [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
USP51 deubiquitinates H2AC20. 1 / 1
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ubibrowser
USP51 deubiquitylates H2AK13,15ub and regulates DNA damage response.
USP51 deubiquitinates H2BC10. 1 / 1
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ubibrowser
In contrast, depletion of non-enzymatic components, ATXN7L3 or ENY2, results in increased H2Bub1. These observations led us to discover two H2Bub1 DUBs, USP27X and USP51, which function independently of SAGA and compete with USP22 for ATXN7L3 and ENY2 for activity.

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
USP51 affects ZEB1
| 1 3
USP51 activates ZEB1.
| 1 2
USP51 activates ZEB1. 3 / 3
| 1 2

eidos
In addition , knockdown of USP51 in A549 / DDP cells significantly induced apoptosis , decreased ZEB1 expression and increased cleaved poly ADP-ribose polymerase 1 ( PARP1 ) and cleaved caspase-3 levels .

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Among DUBs, ubiquitin specific peptidase 51 (USP51) binds to the N-terminal of ZEB1 and increases ZEB1 protein stability in breast cancer cell lines [XREF_BIBR].

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Conversely, overexpression of USP51 in epithelial cells resulted in upregulation of ZEB1 and mesenchymal markers.
USP51 increases the amount of ZEB1.
| 1
USP51 increases the amount of ZEB1. 1 / 1
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In addition, knockdown of USP51 in A549 and DDP cells significantly induced apoptosis, decreased ZEB1 expression and increased cleaved poly ADP-ribose polymerase 1 (PARP1) and cleaved caspase-3 levels.
USP22 affects USP51
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USP22 inhibits USP51.
| 2
USP22 inhibits USP51. 2 / 2
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To determine whether USP22 blocks association of USP27X and USP51 with SAGA, we isolated GCN5 associated proteins after shRNA mediated depletion of USP22.

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To determine whether USP22 blocks association of USP27X and USP51 with SAGA, we isolated GCN5 associated proteins after shRNA mediated depletion of USP22 (XREF_FIG, lanes 2 and 3 and 5 and 6).
USP22 activates USP51.
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USP22 activates USP51. 2 / 2
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Equal numbers of cells expressing shRNAs that specifically target USP27X or USP51, but not USP22 (XREF_FIG), or expressing control shRNA, were seeded and monitored for proliferation by cell counts 72 hours later.

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Equal numbers of cells expressing shRNAs that specifically target USP27X or USP51, but not USP22, or expressing control shRNA, were seeded and monitored for proliferation by cell counts 72 hr later.
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Valproic acid decreases the amount of USP51. 3 / 3
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ctd
No evidence text available

ctd
No evidence text available

ctd
No evidence text available
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Hsa-miR-5011-5p decreases the amount of USP51. 3 / 3
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biopax:mirtarbase
No evidence text available

biopax:mirtarbase
No evidence text available

biopax:mirtarbase
No evidence text available
3 |
Hsa-miR-4798-3p decreases the amount of USP51. 3 / 3
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biopax:mirtarbase
No evidence text available

biopax:mirtarbase
No evidence text available

biopax:mirtarbase
No evidence text available
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Hsa-miR-377-3p decreases the amount of USP51. 3 / 3
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biopax:mirtarbase
No evidence text available

biopax:mirtarbase
No evidence text available

biopax:mirtarbase
No evidence text available
3 |
Hsa-miR-3680-5p decreases the amount of USP51. 3 / 3
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biopax:mirtarbase
No evidence text available

biopax:mirtarbase
No evidence text available

biopax:mirtarbase
No evidence text available
3 |
Hsa-miR-342-3p decreases the amount of USP51. 3 / 3
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biopax:mirtarbase
No evidence text available

biopax:mirtarbase
No evidence text available

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No evidence text available
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Hsa-miR-190a-3p decreases the amount of USP51. 3 / 3
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biopax:mirtarbase
No evidence text available

biopax:mirtarbase
No evidence text available

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No evidence text available
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Hsa-miR-1277-5p decreases the amount of USP51. 3 / 3
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biopax:mirtarbase
No evidence text available

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No evidence text available

biopax:mirtarbase
No evidence text available
USP51 is modified
| 3
USP51 is deubiquitinated. 3 / 3
| 3

trips
CDK4/6 inhibition blocks cancer metastasis through a USP51-ZEB1-dependent deubiquitination mechanism.

trips
Correction to: CDK4/6 inhibition blocks cancer metastasis through a USP51-ZEB1-dependent deubiquitination mechanism.

trips
CDK4/6 inhibition blocks cancer metastasis through a USP51-ZEB1-dependent deubiquitination mechanism.
Nickel atom affects USP51
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Nickel atom decreases the amount of USP51. 2 / 2
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ctd
No evidence text available

ctd
No evidence text available
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Hsa-miR-362-3p decreases the amount of USP51. 2 / 2
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biopax:mirtarbase
No evidence text available

biopax:mirtarbase
No evidence text available
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Hsa-miR-329-3p decreases the amount of USP51. 2 / 2
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biopax:mirtarbase
No evidence text available

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No evidence text available

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In conclusion, suppression of FAT4 by inactivation of deubiquitinating enzyme USP51 promoted proliferation and invasion of EC cells via inhibiting Hippo pathway.

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Knockdown of USP51 decreases the cell proliferation and halts the cell cycle at G0/G1 phase.
CDK4 affects USP51
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CDK4 activates USP51. 2 / 2
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eidos
At the molecular level , CDK4 / 6 phosphorylates and activates USP51 , which is then responsible for the deubiquitination and stabilization of ZEB1 .

eidos
The phosphorylation and activation of USP51 by CDK4 / 6 is necessary to deubiquitinate and stabilize ZEB1 .
6-propyl-2-thiouracil increases the amount of USP51. 2 / 2
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ctd
No evidence text available

ctd
No evidence text available
ZEB1 affects USP51
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ZEB1 decreases the amount of USP51.
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ZEB1 decreases the amount of USP51. 1 / 1
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biopax:msigdb
No evidence text available
ZEB1 activates USP51.
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ZEB1 activates USP51. 1 / 1
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Notably, overexpression of ZEB1 in A549 and DDP cells potently attenuated the effects of USP51 knockdown on apoptosis, and co-IP experiments further demonstrated interaction between USP51 and ZEB.
USP51 affects FAT4
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USP51 increases the amount of FAT4.
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Modified USP51 increases the amount of FAT4. 1 / 1
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Ablating USP51 by shRNA decreased cellular FAT4 protein level while overexpression of USP51 increased FAT4 protein level.
USP51 decreases the amount of FAT4.
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USP51 decreases the amount of FAT4. 1 / 1
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Ablating USP51 by shRNA decreased cellular FAT4 protein level while overexpression of USP51 increased FAT4 protein level.
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Titanium dioxide decreases the amount of USP51. 1 / 1
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ctd
No evidence text available
Thimerosal affects USP51
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Thimerosal decreases the amount of USP51. 1 / 1
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ctd
No evidence text available
Sunitinib affects USP51
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Sunitinib increases the amount of USP51. 1 / 1
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ctd
No evidence text available
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Sodium arsenite increases the amount of USP51. 1 / 1
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ctd
No evidence text available
Silver(0) affects USP51
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Silver(0) decreases the amount of USP51. 1 / 1
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ctd
No evidence text available
Methylmercury chloride decreases the amount of USP51. 1 / 1
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ctd
No evidence text available
Methyl methanesulfonate increases the amount of USP51. 1 / 1
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ctd
No evidence text available
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Hydroquinone decreases the amount of USP51. 1 / 1
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ctd
No evidence text available
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Hsa-miR-95-5p decreases the amount of USP51. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-4719 decreases the amount of USP51. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-4705 decreases the amount of USP51. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-4668-3p decreases the amount of USP51. 1 / 1
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No evidence text available
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Hsa-miR-338-5p decreases the amount of USP51. 1 / 1
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No evidence text available
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Hsa-miR-3163 decreases the amount of USP51. 1 / 1
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No evidence text available
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Hsa-miR-187-5p decreases the amount of USP51. 1 / 1
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biopax:mirtarbase
No evidence text available
Furan affects USP51
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Furan decreases the amount of USP51. 1 / 1
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ctd
No evidence text available
Bisphenol A affects USP51
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Bisphenol A decreases the amount of USP51. 1 / 1
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ctd
No evidence text available
Atrazine affects USP51
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Atrazine increases the amount of USP51. 1 / 1
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ctd
No evidence text available
Abrine affects USP51
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Abrine decreases the amount of USP51. 1 / 1
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ctd
No evidence text available
ZIC1 affects USP51
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ZIC1 decreases the amount of USP51. 1 / 1
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biopax:msigdb
No evidence text available
USP51 affects cell cycle
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Knockdown of USP51 decreases the cell proliferation and halts the cell cycle at G0/G1 phase.
USP51 affects USP
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USP51 inhibits USP. 1 / 1
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These analyses revealed a substantial overlap of altered genes between the depletion of each of the three USPs, including 340 commonly affected genes (p-value 1.1e-130 by Fisher 's exact test) in USP27X and USP51 depleted cells, 283 (p-value 3.3e-34) commonly affected genes in USP22 and USP27X depleted cells, 249 commonly affected genes (p-value 1.1e-74) in USP22 and USP51 depleted cells, and 137 commonly altered genes in all three USP depletions (~ 10% of all altered genes) (XREF_FIG).
USP51 affects TIMM8A
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USP51 activates TIMM8A. 1 / 1
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Collectively, the present findings demonstrated that USP51 inhibition attenuated DDP resistance in A549 and DDP cells via ubiquitin mediated degradation of ZEB1.

eidos
We found that the knockdown of USP51 resulted in significantly decreased lung metastasis ; however , this effect was attenuated in mice carrying ZEB1-expressing tumors ( Fig. 3e , f ) , confirming that the knockdown of USP51 reduces cancer metastasis through the regulation of ZEB1 in vivo .
USP51 affects Histone
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USP51 activates Histone. 1 / 1
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Examination of the Deubiquitylation Site Selectivity of USP51 by Using Chemically Synthesized Ubiquitylated Histones.

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USP51 depletion results in increased spontaneous DNA damage foci and elevated levels of H2AK15ub and impairs DNA damage response.
USP51 affects DGCR8
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USP51 activates DGCR8. 1 / 1
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Upon radiation, the kinase ATM and the deubiquitinase USP51 mediate the activation and stabilization of DGCR8 through phosphorylation and deubiquitination.
MAZ affects USP51
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MAZ decreases the amount of USP51. 1 / 1
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biopax:msigdb
No evidence text available
HNF4A affects USP51
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HNF4A decreases the amount of USP51. 1 / 1
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biopax:msigdb
No evidence text available
HAND1 affects USP51
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HAND1 decreases the amount of USP51. 1 / 1
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biopax:msigdb
No evidence text available
ESRRA affects USP51
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ESRRA decreases the amount of USP51. 1 / 1
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biopax:msigdb
No evidence text available
ENY2 affects USP51
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ENY2 deubiquitinates USP51. 1 / 1
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Our results now reveal that in addition to USP22, ATXN7L3 and ENY2 activate two previously uncharacterized deubiquitinating enzymes, USP27X and USP51, which are not part of SAGA.
ATXN7L3 affects USP51
| 1
ATXN7L3 deubiquitinates USP51. 1 / 1
| 1

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Our results now reveal that in addition to USP22, ATXN7L3 and ENY2 activate two previously uncharacterized deubiquitinating enzymes, USP27X and USP51, which are not part of SAGA.