USP7 Data Analysis

HGNC Gene Name
ubiquitin specific peptidase 7
HGNC Gene Symbol
USP7
Identifiers
hgnc:12630 NCBIGene:7874 uniprot:Q93009
Orthologs
mgi:2182061 rgd:1306915
INDRA Statements
deubiquitinations all statements
Pathway Commons
Search for USP7
Number of Papers
627 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
MDM2 MDM2 proto-oncogene 0.499 BioGRID IntAct Pathway Commons INDRA (37) Reactome (14) 0.17 0.82 3.76e-02
TP53 tumor protein p53 -0.44 BioGRID IntAct Pathway Commons INDRA (49) Reactome (16) -0.01 -0.16 8.62e-01
PPM1D protein phosphatase, Mg2+/Mn2+ dependent 1D 0.4 Reactome (3) 0.11 0.54 2.79e-01
TP53BP1 tumor protein p53 binding protein 1 -0.377 IntAct INDRA (1) Reactome (3) 0.01 -0.01 8.49e-01
C16orf72 chromosome 16 open reading frame 72 0.359 0.34 1.81 6.71e-04
CDKN1A cyclin dependent kinase inhibitor 1A -0.342 INDRA (5) Reactome (7) -0.01 -0.12 9.48e-01
USP28 ubiquitin specific peptidase 28 -0.331 INDRA (1) Reactome (4) 0.16 0.79 6.28e-03

Dependency GO Term Enrichment

Gene set enrichment analysis was done on the genes correlated with USP7using 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:0010212 response to ionizing radiation Biological Process 1.61e-10 8.11e-08 9.67e-09
GO:0009314 response to radiation Biological Process 1.68e-10 8.45e-08 9.67e-09
GO:0031570 DNA integrity checkpoint Biological Process 2.24e-10 1.13e-07 9.67e-09
GO:0071478 cellular response to radiation Biological Process 5.69e-10 2.87e-07 1.84e-08
GO:0000075 cell cycle checkpoint Biological Process 1.09e-09 5.47e-07 2.81e-08
GO:0071479 cellular response to ionizing radiation Biological Process 2.68e-09 1.35e-06 5.72e-08
GO:0072331 signal transduction by p53 class mediator Biological Process 3.09e-09 1.56e-06 5.72e-08
GO:0034644 cellular response to UV Biological Process 4.15e-09 2.09e-06 6.71e-08
GO:0071214 cellular response to abiotic stimulus Biological Process 8.08e-09 4.07e-06 1.16e-07
GO:0030330 DNA damage response, signal transduction by p53 class mediator Biological Process 1.37e-08 6.90e-06 1.77e-07
GO:0071482 cellular response to light stimulus Biological Process 2.93e-08 1.48e-05 3.45e-07
GO:0042770 signal transduction in response to DNA damage Biological Process 3.32e-08 1.67e-05 3.58e-07
GO:0009411 response to UV Biological Process 3.97e-08 2.00e-05 3.96e-07
GO:0031668 cellular response to extracellular stimulus Biological Process 5.54e-07 2.79e-04 5.12e-06
GO:0097193 intrinsic apoptotic signaling pathway Biological Process 7.61e-07 3.84e-04 5.80e-06
GO:0002039 p53 binding Molecular Function 7.62e-07 3.84e-04 5.80e-06
GO:0009416 response to light stimulus Biological Process 1.05e-06 5.28e-04 7.54e-06
GO:0072395 signal transduction involved in cell cycle checkpoint Biological Process 1.13e-06 5.69e-04 7.70e-06
GO:0072332 intrinsic apoptotic signaling pathway by p53 class mediator Biological Process 1.27e-06 6.42e-04 8.25e-06
GO:0071496 cellular response to external stimulus Biological Process 1.39e-06 7.02e-04 8.58e-06
GO:0071158 positive regulation of cell cycle arrest Biological Process 1.54e-06 7.77e-04 9.07e-06
GO:0090400 stress-induced premature senescence Biological Process 2.33e-06 1.18e-03 1.31e-05
GO:0071156 regulation of cell cycle arrest Biological Process 3.54e-06 1.79e-03 1.83e-05
GO:0044774 mitotic DNA integrity checkpoint Biological Process 3.44e-06 1.74e-03 1.83e-05
GO:1902807 negative regulation of cell cycle G1/S phase transition Biological Process 6.19e-06 3.12e-03 3.08e-05
GO:0090399 replicative senescence Biological Process 7.57e-06 3.82e-03 3.63e-05
GO:0009267 cellular response to starvation Biological Process 9.52e-06 4.80e-03 4.40e-05
GO:0007093 mitotic cell cycle checkpoint Biological Process 1.27e-05 6.39e-03 5.66e-05
GO:0046827 positive regulation of protein export from nucleus Biological Process 1.75e-05 8.80e-03 7.53e-05
GO:0042594 response to starvation Biological Process 1.84e-05 9.29e-03 7.58e-05
GO:0006367 transcription initiation from RNA polymerase II promoter Biological Process 1.87e-05 9.44e-03 7.58e-05
GO:1902806 regulation of cell cycle G1/S phase transition Biological Process 2.25e-05 1.14e-02 8.84e-05
GO:0071480 cellular response to gamma radiation Biological Process 3.37e-05 1.70e-02 1.28e-04
GO:0010165 response to X-ray Biological Process 3.86e-05 1.95e-02 1.43e-04
GO:0097718 disordered domain specific binding Molecular Function 4.12e-05 2.07e-02 1.44e-04
GO:0007050 cell cycle arrest Biological Process 4.08e-05 2.06e-02 1.44e-04
GO:0006352 DNA-templated transcription, initiation Biological Process 4.34e-05 2.19e-02 1.48e-04
GO:1901988 negative regulation of cell cycle phase transition Biological Process 5.22e-05 2.63e-02 1.73e-04
GO:0044839 cell cycle G2/M phase transition Biological Process 5.46e-05 2.75e-02 1.77e-04
GO:0031647 regulation of protein stability Biological Process 5.90e-05 2.97e-02 1.86e-04
GO:0046825 regulation of protein export from nucleus Biological Process 6.47e-05 3.26e-02 1.99e-04
GO:0044843 cell cycle G1/S phase transition Biological Process 7.04e-05 3.55e-02 2.12e-04
GO:0090068 positive regulation of cell cycle process Biological Process 7.33e-05 3.70e-02 2.15e-04
GO:0070646 protein modification by small protein removal Biological Process 7.48e-05 3.77e-02 2.15e-04
GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Biological Process 7.84e-05 3.95e-02 2.21e-04
GO:0044389 ubiquitin-like protein ligase binding Molecular Function 8.01e-05 4.04e-02 2.21e-04
GO:2000379 positive regulation of reactive oxygen species metabolic process Biological Process 8.57e-05 4.32e-02 2.31e-04

Transcriptomics

The following table shows the significantly differentially expressed genes after knocking out USP7 using CRISPR-Cas9.

Knockout Differential Expression

Symbol Name log2-fold-change p-value p-value (adj.)
PYGL glycogen phosphorylase L 7.07e-01 1.63e-08 8.78e-05
IFIT3 interferon induced protein with tetratricopeptide repeats 3 6.41e-01 1.29e-07 3.48e-04
SF3B6 splicing factor 3b subunit 6 4.14e-01 1.98e-07 3.55e-04
MMP1 matrix metallopeptidase 1 3.86e-01 2.87e-07 3.86e-04
DFFA DNA fragmentation factor subunit alpha 5.26e-01 1.37e-06 1.48e-03
PGK1 phosphoglycerate kinase 1 -3.65e-01 3.77e-06 3.38e-03
LDHA lactate dehydrogenase A -3.46e-01 9.03e-06 6.94e-03
USP7 ubiquitin specific peptidase 7 -1.06e+00 1.23e-05 8.27e-03
PTBP1 polypyrimidine tract binding protein 1 6.91e-01 3.52e-05 1.84e-02
S100A2 S100 calcium binding protein A2 -6.33e-01 3.77e-05 1.84e-02
SAA2 serum amyloid A2 -7.78e-01 3.29e-05 1.84e-02
FAM136A family with sequence similarity 136 member A 3.86e-01 4.80e-05 2.16e-02
GLO1 glyoxalase I 3.68e-01 5.70e-05 2.36e-02
MT-ND6 mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 6 -5.88e-01 9.12e-05 3.51e-02
ANKRD1 ankyrin repeat domain 1 3.05e-01 1.45e-04 4.91e-02
IGFBP4 insulin like growth factor binding protein 4 -2.98e-01 1.46e-04 4.91e-02

Gene Set Enrichment Analysis

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

Literature Mining

INDRA was used to automatically assemble known mechanisms related to USP7 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
USP7 deubiquitinates TP53. 10 / 75
1 | 73

reach
Usp7 directly deubiquitinates and stabilises p53, it is also necessary for p53 stabilisation by the tumour suppressor ING1 [XREF_BIBR].

reach
Because HAUSP can deubiquitinate both p53 and Mdm2, the dynamic consequences are not straightforward.

reach
While the E3-ligase MDM2 ubiquitinates p53 to induce its proteasomal degradation, HAUSP deubiquitinates P53 and stabilizes the protein.

reach
Interestingly, in response to oncogenic insults, HAUSP can deubiquitinate p53 and protect p53 from MDM2 mediated degradation of p53 in response to stress.

reach
This result indicates that ABRO1 specifically facilitates USP7 mediated deubiquitination of p53.

reach
USP7 deubiquitinates several tumour suppressors (p53, PTEN, FOXO and claspin) and E3 ligases (MDM2, Mule and viral proteins ICP0) and therefore regulates important signalling pathways that are involved in tumorigenesis XREF_BIBR XREF_BIBR.

reach
The observation that HAUSP can directly interact with and deubiquitylate both p53 and MDM2 creates a conundrum : how can HAUSP stabilize p53 while at the same time being able to stabilize MDM2, which is primarily responsible for the destruction of p53?

reach
XREF_BIBR - XREF_BIBR USP7 deubiquitinates and stabilizes not only p53, but also Mdm2, the primary E3 ubiquitin ligase of p53 XREF_BIBR, XREF_BIBR Given that both p53 and Mdm2 are known regulators of the steady-level of Poleta, we speculated that changes in cellular USP7 levels may also modulate Poleta level.

reach
USP7 preferentially deubiquitylates the E3 ligase HDM2 and its binding partner HDMX as well as their substrate p53 (Brooks et al., 2007; Cummins and Vogelstein, 2004; Li et al., 2002, 2004; Meulmeeste[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

reach
Further, in vitro assays have shown that MDM2 may act as a bridge so that deubiquitination of p53 by USP7 can occur in the absence of a direct interaction between the two proteins [XREF_BIBR].
USP7 deubiquitinates MDM2. 10 / 61
1 | 1 58

reach
However, Mdm2 can also self-ubiquitylate which promotes its own degradation therefore releasing p53 from its regulatory control, although this is inhibited by USP7, which persistently deubiquitylates Mdm2.

reach
Thus USP7 would be posited to have opposing effects depending on whether it predominantly deubiquitinates and rescues p53 or MDM2.

reach
Importantly, HAUSP can deubiquitinate MDM2, MDMX, and p53.

reach
USP7 deubiquitinates both p53 and MDM2, one of the ubiquitin ligases that ubiquitylates p53, thereby stabilizing both proteins [XREF_BIBR, XREF_BIBR].

reach
USP7 preferentially deubiquitylates the E3 ligase HDM2 and its binding partner HDMX as well as their substrate p53 (Brooks et al., 2007; Cummins and Vogelstein, 2004; Li et al., 2002, 2004; Meulmeeste[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

reach
USP7, an MDM2 deubiquitinase, deubiquitinates MDM2 and prolongs its half-life to inhibit the p53 tumor suppressor function [XREF_BIBR].

reach
These contradictory findings were explained by the fact that USP7 could also deubiquitylate MDM2 in some settings, thus indirectly leading to p53 degradation.

reach
However, HAUSP also deubiquitinates MDM2 and reduction of HAUSP levels, either by RNA interference or by gene deletion, produces a complex phenotype [XREF_BIBR - XREF_BIBR].

reach
A lack of USP7 dependent deubiquitylation of MDM2 may lead, through enhanced breakdown of MDM2, to accumulation of p53 in melanoma.

reach
Interestingly, USP7 can deubiquitinate both p53 and its negative regulator HDM2, an E3 ubiquitin ligase responsible for polyubiquitination and subsequent degradation of p53.
USP7 deubiquitinates Histone_H2B. 10 / 22
| 22

reach
These results are consistent with GMPS stimulating deubiquitylation of H2B by USP7 by forming a stoichiometric complex with USP7 and are inconsistent with GMPS acting catalytically.

reach
We have observed that USP7 silencing increases H2B ubiquitylation at the FR as well as at LMP1 and Cp promoters and decreases transcriptional activation from the FR element, suggesting that H2B ubiquitylation is inhibitory to transcription controlled by the FR.

reach
USP7 deubiquitinates H2A and H2B in vitro and changes in Bmi1 and Ring1 ubiquitin levels were reported in USP7 and USP11 overexpression lines.

reach
This prompted us to investigate whether the human USP7 and GMPS complex also functioned to deubiquitylate histone H2B.

reach
EBNA1 can also recruit USP7 to EBV sequences that regulate viral gene expression and genome persistence where, in complex with GMP synthetase, USP7 can deubiquitylate histone H2B and affect EBNA1 mediated transcriptional activation XREF_BIBR.

reach
GMPS enables USP7 dependent deubiquitination of histone H2B resulting in epigenetic silencing [XREF_BIBR - XREF_BIBR].

reach
In addition to USP22 and its yeast homolog, H2B can be deubiquitylated by USP3 and USP7 in humans.

reach
The effect of USP7 on deubiquitination of H2A is most likely indirect, since USP7 selectively deubiquitinates histone H2B, but not H2A [XREF_BIBR].

reach
If the USP7 and GMPS complex functions to deubiquitylate histone H2B, then the loss of this complex from the FR would be expected to increase the level of Ub-H2B in this region.

reach
GMP synthetase stimulates histone H2B deubiquitylation by the epigenetic silencer USP7.
USP7 deubiquitinates PTEN. 10 / 19
| 1 17

reach
However, PTEN is deubiquitinated by USP7/HAUSP and released to the cytoplasm on the PML-RARα signaling network [24].
| PMC

reach
XREF_BIBR, XREF_BIBR, XREF_BIBR The DUB USP7 can reverse PTEN monoubiquitylation, affecting its cellular localization; 28 however, to date no DUBs have been described that reverse PTEN polyubiquitylation or otherwise influence PTEN expression levels.

reach
More recently, the ability of USP7 to deubiquitinate PTEN was found to be under the control of BCR-ABL.

reach
HAUSP deubiquitinates PTEN to cause its nuclear exclusion, leading to tumour aggressiveness XREF_BIBR.

reach
HAUSP deubiquitinates monoubiquitinated nuclear PTEN, facilitating nuclear exclusion of PTEN and promoting cancer progression in prostate cancer.

reach
245 HAUSP (herpesvirus associated ubiquitin specific protease) deubiquitinates PTEN in the nucleus.

ubibrowser
Review

reach
On the other hand, reversal of PTEN monoubiquitination by USP7 (also known as HAUSP) alters PTEN subcellular localization without affecting its protein level [XREF_BIBR].

reach
We have demonstrated that PTEN monoubiquitination at lysines 13 and 289 is essential for its nuclear localization and tumor suppressive function and, conversely, deubiquitination of PTEN by HAUSP renders PTEN predominantly cytoplasmic.

reach
A PTEN deubiquitinating enzyme, HAUSP (herpesvirus associated ubiquitin specific protease) may serve in the deubiquitination of PTEN and its shuttling out of the nucleus.
USP7 deubiquitinates DNMT1. 10 / 12
| 11

reach
Conversely, HDAC1 (histone deacetylase 1) induced DNMT1 deacetylation and HAUSP (herpes virus associated ubiquitin specific protease) modulated DNMT1 deubiquitination to stabilize DNMT1 44.

reach
We recently showed that USP7 deubiquitinates DNMT1 and functions in concert with several other proteins to regulate DNMT1 stability.

reach
The UHRF1 and DNMT1 complex has been reported to contain USP7 that deubiquitinates and stabilizes DNMT1 XREF_BIBR, XREF_BIBR.

reach
Together, these observations suggest that multistep posttranslational modification events may be required to dissociate the UHRF1 and USP7 complex during M phase.Recent evidence has indicated that USP[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

reach
Recent evidence has indicated that USP7 also deubiquitinates DNMT1 during S-phase; in late S-phase, acetylation of DNMT1 by Tip60 leads to disruption of the DNMT1 and USP7 complex.

reach
Importantly, both HDAC3 and USP7 decreased DNMT1 ubiquitination (XREF_FIG, DNMT1 IP).

reach
FA decreased the ubiquitination of DNMT1 (p = 0.0753), DNMT3A (p = 0.0008) and DNMT3B (p < 0.0001) by decreasing UHRF1 (p < 0.0001) and USP7 (p < 0.0001).

reach
HAUSP deubiquitinates DNMT1 and protects it from proteasomal degradation.

ubibrowser
Review

reach
Consistent with previous studies that USP7 deubiquitinates and stabilizes DNMT1, knockdown of USP7 in several cell lines (HEK293T, HeLa, HCT116 p53-/- and p53 +/+ cells) resulted in a significant decrease in the DNMT1 protein level, but not in the DNMT1 messenger RNA level (XREF_FIG and XREF_SUPPLEMENTARY).
USP7 deubiquitinates REST. 10 / 11
| 10

reach
To further address whether REST deubiquitination is directly and specifically mediated by HAUSP, we performed an in vitro deubiquitination assay XREF_BIBR with purified wild-type HAUSP (Flag-Wt-HAUSP), catalytic dead mutant HAUSP (Flag-Mt-HAUSP), or a control deubiquitinase USP1 (Flag-USP1).

reach
These data further support that REST deubiquitination is specifically mediated by HAUSP.

ubibrowser
Collectively, our data demonstrate that the hTPH2 NRSE-mediated promoter repression via NRSF involves class I HDACs and is modulated by the ubiquitin-specific protease 7-mediated deubiquitination and stabilization of NRSF.

reach
Wt-HAUSP specifically counteracted beta-TrCP-mediated REST ubiquitination, while the Mt-HAUSP or the control deubiquitinase USP1 did not alter the REST ubiquitination (XREF_FIG), suggesting that HAUSP directly and specifically deubiquitinated REST and suppressed REST ubiquitination.

reach
We determined that HAUSP physically interacts with REST as demonstrated in co-immunoprecipitation assays (XREF_FIG; XREF_SUPPLEMENTARY), suggesting that HAUSP may mediate REST deubiquitination to prevent REST proteosomal degradation.

reach
We hypothesized that HAUSP functions as a critical counterbalance to beta-TrCP to inhibit REST ubiquitination and maintain NPCs.

reach
Collectively, these data demonstrate that HAUSP negatively regulates REST ubiquitination and promotes REST stabilization.

reach
Our data demonstrate that HAUSP directly deubiquitinates REST.

reach
Thus, we have identified the consensus HAUSP binding site (310-PYSS-313) on human REST that is required for the HAUSP mediated REST deubiquitination.

reach
HAUSP knockdown increased REST poly-ubiquitination as demonstrated by both anti-REST immunoprecipitation (IP) and anti-Ubiquitin reciprocal IP (XREF_FIG; XREF_SUPPLEMENTARY).
USP7 deubiquitinates KAT5. 10 / 11
| 1 9

reach
Deubiquitination of Tip60 by USP7 determines the activity of the p53-dependent apoptotic pathway.

ubibrowser
USP7 deubiquitinates and stabilizes the acetyltransferase Tip60 to induce p53-dependent apoptotic pathways

reach
As ATF3 appears to bind to MDM2 as well as p53 XREF_BIBR, XREF_BIBR, the observation that ATF3 promoted USP7 mediated deubiquitination of Tip60 suggests a possibility that ATF3 might also regulate the MDM2 or p53 stability through regulating USP7 in the DNA damage response.

reach
ATF3 promotes USP7 mediated deubiquitination of Tip60.

reach
As ATF3 alone did not appear to decrease the Tip60 ubiquitination level (XREF_FIG, lane 3), these results argue for the notion that ATF3 promoted USP7 mediated deubiquitination of Tip60 thereby stabilizing the latter protein.

trips
Deubiquitination of Tip60 by USP7 determines the activity of the p53-dependent apoptotic pathway.

reach
Rather, we found that ATF3 promoted USP7 mediated deubiquitination of Tip60 thereby diminishing Tip60 ubiquitination required for proteosomal degradation.

reach
In addition, utilizing the UbiTest analysis we demonstrate that inhibition of USP7 increases polyubiquitination of Foxp3, Tip60 and USP7.

reach
Here we show that USP7 interacts with and deubiquitinates Tip60 both in vitro and in vivo.

reach
USP7, a dominant deubiquitinating enzyme in 3T3-L1 adipocytes and mouse adipose tissue, deubiquitinates Tip60 both in intact cells and in vitro and increases Tip60 protein levels.
USP7 deubiquitinates FOXP3. 10 / 10
| 9

reach
On the other hand, the deubiquitinase USP7 is able to deubiquitinate FOXP3 in an HSP90 dependent manner and stabilizes FOXP3 to increase Treg number to enhance Treg suppressive activity.

reach
USP7 Associates with and Deubiquitinates Foxp3.

ubibrowser
Furthermore, cambogin (10 μM) prevented Foxp3 loss in human primary Treg cells in vitro, and promoted USP7-mediated Foxp3 deubiquitination and increased Foxp3 protein expression in LPS-treated cells.

reach
To determine whether USP7 could also deubiquitinate Foxp3, we analyzed Foxp3 polyubiquitination in transfected HEK 293T cells.

reach
E3 ubiquitin ligase Stub1 induces the K48 polyubiquitination and degradation of Foxp3, whereas deubiquitinase USP7 decreases Foxp3 polyubiquitination and increases Foxp3 expression XREF_BIBR.

reach
USP7 mRNA expression was significantly upregulated in iTreg cells but not in other Th subsets, further supporting a role for the USP7 deubiquitination of Foxp3 in Treg cell differentiation (XREF_FIG).

reach
In a previous study, van Loosdregt et al. (2013) showed that USP7 interacted with and deubiquitinated Foxp3, thereby increasing Foxp3 protein levels.

reach
Conversely, the DUB Usp7 deubiquitinates and stabilizes Foxp3 to promote Treg functions.

reach
In addition, utilizing the UbiTest analysis we demonstrate that inhibition of USP7 increases polyubiquitination of Foxp3, Tip60 and USP7.

reach
Foxp3 polyubiquitination was reduced with ectopic expression of USP7, indicating that USP7 can directly deubiquitinate Foxp3 (XREF_FIG).
USP7 deubiquitinates MDM4. 10 / 10
1 | 1 7

ubibrowser
Review

reach
USP7 preferentially deubiquitylates the E3 ligase HDM2 and its binding partner HDMX, resulting in the destabilisation of p53 and the repression of p53 transactivation activity (Refs 43, 44, 45).

trips
Subsequently, HAUSP was shown to deubiquitinate Mdm2 and Mdmx, thereby stabilizing these proteins.

reach
More recent data suggest that Hausp also deubiquitinates Mdm4, another inhibitor of p53 activity.

reach
Additionally, Wip1 inhibits p53 through MdmX and enhances the interaction of MdmX with ubiquitin specific peptidase 7 (USP7), which deubiquitinates and stabilizes MdmX.

reach
Additionally, Mdm2, MdmX and p53 can be deubiquitinated by the HAUSP (herpesvirus associated ubiquitin specific protease) protein.

reach
Importantly, HAUSP can deubiquitinate MDM2, MDMX, and p53.

reach
MdmX phosphorylation (A38) inhibits (A40) the deubiquitination (A39) of MdmX by Hausp, which in turn increases ubiquitinated MdmX showing coherent regulation by DNA damage induced kinases.

reach
HAUSP can also deubiquitinate and stabilize MdmX and has a role in DNA damaged induced degradation of MdmX [XREF_BIBR].

signor
Subsequently, hausp was shown to deubiquitinate mdm2 and mdmx, thereby stabilizing these proteins.
USP7 deubiquitinates CTNNB1. 10 / 10
| 9

reach
Conversely, USP7 promotes deubiquitination of beta-catenin with RNF220, which is a RING domain E3 ligase, and upregulates the Wnt signaling pathway [XREF_BIBR].

reach
Indeed, CRISPR targeting of USP7 in the CID deleted APC4 cells readily restored beta-catenin ubiquitination in the destruction complex (XREF_FIG D and XREF_SUPPLEMENTARY I).

reach
Moreover, ZMIZ2 recruits the enzyme USP7, which deubiquitylates and stabilizes beta-catenin, thereby facilitating colorectal tumorigenesis.

ubibrowser
USP7 Is a Tumor-Specific WNT Activator for APC-Mutated Colorectal Cancer by Mediating β-Catenin Deubiquitination

reach
Specifically, USP7 binds the N-terminus of β-catenin when the APC losses CID confirming the essential role of USP7 in the activation of Wnt signalling and cell survival in colorectal cancers.13 Ma et al showed that the USP7/RNF220 complex activates the Wnt pathway while knockdown of USP7 using a small interfering RNA (siRNA) strategy, reduces the expression of Wnt.18 Conversely, a recent study proposed that USP7 deubiquitinates β-catenin and RNF220 independently and works as a tumour-specific condition when APC is mutated.
| PMC

reach
USP7 Depletion in APC Truncated CRC Cells Suppresses Aberrant Wnt Activation by Restoring beta-Catenin Ubiquitination.

reach
Ubiquitin specific peptidase 7 (USP7) mediates deubiquitination of beta-catenin and enhances canonical Wnt signaling [XREF_BIBR].

reach
Together, our data imply that USP7 interacts with the N terminus of beta-catenin directly to mediate beta-catenin deubiquitination when APC is mutated.

reach
The RNF220 and USP7 complex deubiquitinates beta-catenin and enhances canonical Wnt signaling.

reach
USP7 Interacts with the N Terminus of beta-Catenin Directly to Mediate beta-Catenin Deubiquitination.
USP7 deubiquitinates ERCC6. 9 / 9
| 8

reach
While both CSB and UV stimulated scaffold protein A (UVSSA) exhibit a biphasic decrease and recovery upon UV irradiation, only CSB recovery depends on USP7, which physically interacts with and deubiquitinates CSB.

reach
Additional factors continue to be identified : Examples include NEDD4, that is implicated in DNA damage induced ubiquitination of the RNA polymerase II subunit RPB1 to mark it for proteosomal degradat[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

ubibrowser
Review

reach
Upon transcription arrest, these factors bind strongly to RNAPII, and USP7 deubiquitinates CSB to stabilize it.

reach
Upon transcription arrest, these factors bind strongly to RNAPII, and USP7 deubiquitylates CSB to stabilize it.

reach
Additional factors continue to be identified : Examples include NEDD4, that is implicated in DNA damage induced ubiquitination of the RNA polymerase II subunit RPB1 to mark it for proteosomal degradation; UVSSA and USP7 that bind to RNAPII upon transcription arrest and deubiquitinate CSB to prevent its degradation; and the SPT16 FACT chromatin remodeler.

reach
Upon transcription arrest, these factors bind strongly to RNAPII, and USP7 deubiquitylates CSB to stabilize it.

reach
To avoid premature degradation of CSB, UVSSA, which binds firmly to stalled RNA pol II, recruits USP7, an enzyme that promotes deubiquitination of CSB, highlighted in blue in XREF_FIG.

reach
Here, we demonstrate that USP7 deubiquitinates CSB to maintain its levels after ultraviolet (UV)-induced DNA damage.
USP7 deubiquitinates HIF1A. 8 / 8
| 7

reach
USP7, also known as HAUSP (herpesvirus associated ubiquitin specific protease), deubiquitinates HIF-1alpha and stabilizes it.

reach
Beyond, USP7 deubiquitinates and stabilizes HIF1alpha, PHF8 could regulate HIF1alpha through USP7 [XREF_BIBR].

reach
K63 polyubiquitinated HAUSP deubiquitinates HIF-1alpha and dictates H3K56 acetylation promoting hypoxia induced tumour progression.

reach
Since both HAUSP and HIF-1alpha play a significant role in tumour progression and aggressiveness XREF_BIBR XREF_BIBR, we evaluated whether HAUSP could deubiquitinate HIF-1alpha through interacting with HIF-1alpha.

reach
HAUSP interacts with and deubiquitinates HIF-1alpha.

reach
Beyond, USP7 deubiquitinates and stabilizes HIF1alpha, PHF8 could regulate HIF1alpha through USP7 [49].

reach
These results demonstrate that HAUSP decreases HIF-1alpha ubiquitination through recognizing a consensus sequence located in HIF-1alpha.

ubibrowser
K63-polyubiquitinated HAUSP deubiquitinates HIF-1a and dictates H3K56 acetylation promoting hypoxia-induced tumour progression.
USP7 deubiquitinates TPP1. 7 / 7
| 6

reach
Together, these data indicate that USP7 deubiquitinates TPP1.

reach
Addition of USP7 (WT)-3xFLAG but not USP7 (C223S)-3xFLAG reduced TPP1 ubiquitination (XREF_FIG C, lanes 5 and 6), confirming that TPP1 is a USP7 substrate.

reach
We identify amino acids in TPP1 and USP7 that are critical for their interaction and multiple lysines within TPP1 that are oligo ubiquitinated and deubiquitinated by USP7.

reach
Therefore, both in vivo and in vitro evidence indicates that TPP1 is deubiquitinated by USP7.

reach
TPP1 Is Deubiquitinated by USP7.

ubibrowser
Review

reach
Because TPP1 is ubiquitinated and the co-immunoprecipitation data suggested that it is a USP7 substrate, we next tested whether USP7 indeed deubiquitinates TPP1.
USP7 deubiquitinates RNF2. 7 / 7
| 6

reach
Taken together, these data indicate that USP7 specifically deubiquitinates RING1B in vitro.

reach
In order to confirm that USP7 mediates the deubiquitination of RING1B, we added to self ubiquitinated RING1B bacterially expressed purified His 6 -USP7 and its inactive mutant His 6 -USP7 C223S.

reach
Although, USP7 directly and specifically deubiquitinates RING1B in vitro and in vivo, it does not discriminate between the activating and proteolysis targeting modes of ubiquitination, and therefore has a stabilizing effect on RING1B.

reach
USP7 deubiquitinates ubiquitinated (by itself or external ligase such as E6AP) RING1B ligase of the polycomb complex [XREF_BIBR].

reach
As shown in Fig. 4 C, USP7 is not a chain type specific DUB and it can deubiquitinate different lysine based polyubiquitin chains.Based on our observation that USP7 can reverse E6-AP-mediated ubiquiti[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

ubibrowser
Here we identify USP7 as a deubiquitinating enzyme that regulates the ubiquitination state of RING1B.

reach
It is possible that in wild type spermatocytes, USP7 may directly deubiquitinate RNF2 and thus reduce H2A ubiquitination in the XY body.
USP7 deubiquitinates NFkappaB. 7 / 7
| 7

reach
NFkappaB can be directly deubiquitinated by HAUSP 87 or can be indirectly regulated by deubiquitination of its upstream factors, such as TRAF6, 24 NEMO (IKK-gamma) XREF_BIBR, XREF_BIBR (HSCARG interacts with NEMO to suppress its polyubiquitination by recruiting HAUSP 91), NIMA (Never In Mitosis Gene A)-related kinase 2 (Nek2), a centrosomal serine/threonine kinase (HAUSP stabilizes Nek2 leading to activation of NFkappaB pathway in multiple myeloma).

reach
USP7 deubiquitination of NF-kappaB leads to increased transcription.

reach
Therefore, USP7 's deubiquitination of NF-kappaB enhances pro cytokine production when induced by the TLR signaling pathway.

reach
This analysis reveals a significant and selective inhibition of NF-kB target gene expression following TLR4 activation and strongly supports the inhibition of USP7 deubiquitination of NF-kB as a potential therapeutic strategy.

reach
Moreover, USP7 deubiquitination of NF-kappaB subunits leads to the increase of transcriptional activity, suggesting this may be the mechanism by which P22077 inhibits H 2 O 2 -induced USP7 mRNA expression.

reach
It has been reported that deubiquitination of NF-kappaB by USP7 is essential for TLR- and TNFR induced gene expression [XREF_BIBR], thus USP7 may has a positive feedback in regulating TNFR1 and also circ-DB formation.

reach
These findings reveal a unique mechanism controlling NF-kappaB activity and demonstrate that the deubiquitination of NF-kappaB by USP7 is critical for target gene transcription.
USP7 deubiquitinates SPRTN. 6 / 6
| 6

reach
USP7 deubiquitinase deubiquitinates SPRTN upon DPC induction, antagonizing the autocatalytic cleavage and subsequent inactivation of SPRTN.

reach
Upon formaldehyde treatment and other yet to be identified signals, SPRTN is deubiquitinated by USP11 (this study), USP7, and VCPIP1.

reach
USP7 deubiquitylates SPRTN upon DPC induction.

reach
Recently, it was shown that USP7 deubiquitinates SPRTN, preventing SPRTN auto-cleavage upon DPC induction.

reach
Upon DPC induction, SPRTN is deubiquitinated by USP7, promoting SPRTN stability.

reach
showed that deubiquitination of SPRTN by USP7 does not govern SPRTN localization on chromatin.
USP7 deubiquitinates CHEK1. 6 / 6
| 4

reach
Here we identified ZEB1 as an ATM substrate and the mechanism underlying the association between EMT and radioresistance (XREF_FIG) : in response to IR, ATM kinase is activated, which phosphorylates and stabilizes ZEB1; ZEB1 in turn interacts with and promotes the activity of USP7, which deubiquitinates and stabilizes CHK1.

reach
68 HAUSP deubiquitinates checkpoint kinase Chk1, 69 its activator Claspin, 70 and checkpoint with forkhead and RING finger domain protein (Chfr).

reach
Mechanistically, LINC02582 interacts with deubiquitinating enzyme ubiquitin specific peptidase 7 (USP7) to deubiquitinate and stabilize checkpoint kinase 1 (CHK1), a critical effector kinase in DNA damage response, thus promoting radioresistance.

ubibrowser
Mechanistically, LINC02582 interacts with deubiquitinating enzyme ubiquitin specific peptidase 7 (USP7) to deubiquitinate and stabilize checkpoint kinase 1 (CHK1), a critical effector kinase in DNA damage response, thus promoting radioresistance.

ubibrowser
Review

reach
USP7 purified from 293T cells transfected with USP7 alone decreased CHK1 poly-ubiquitination by 25% in vitro, and USP7 and ZEB1 co-purified from 293T cells with co-transfection of USP7 and ZEB1 reduced CHK1 poly-ubiquitination by 43% (XREF_FIG).
USP7 deubiquitinates ANXA1. 6 / 6
| 6

reach
In this regard, we suggest that deubiquitination of ANXA1 by HAUSP is essential for UV induced damage responsive function of ANXA1.

reach
The result showed that HAUSP could reduce the ANXA1 ubiquitination level more upon UV, possibly due to the increase in HAUSP-ANXA1 binding.

reach
Collectively, our data suggest that the deubiquitination of ANXA1 is specifically mediated by HAUSP, and HAUSP mediated deubiquitination of ANXA1 may be important for ANXA1 's damage response function in the nucleus upon UV.

reach
In this regard, our result of immunofluorescence analysis in HAUSP KD HeLa cells, which showed translocation of nuclear ANXA1 to the cytosol (XREF_FIG), may be due to the failure of deubiquitination of ANXA1 mediated by HAUSP.

reach
These data suggest that deubiquitination of ANXA1 by HAUSP is essential for the UV induced damage response function of ANXA1 in Jurkat cells.

reach
Deubiquitination of ANXA1 by HAUSP regulates UV induced damage response in HeLa cells.
USP7 deubiquitinates CLSPN. 5 / 5
| 4

reach
Because extracts from mitotic cells readily support ubiquitylation of Claspin in a betaTrCP dependent fashion, we used such an approach to test whether USP7 directly deubiquitylates Claspin in vitro.

reach
In contrast, little if any effect on Claspin stability was evident in cells expressing USP7 CI (XREF_FIG), which supports the idea that Claspin is deubiquitylated by USP7.

reach
68 HAUSP deubiquitinates checkpoint kinase Chk1, 69 its activator Claspin, 70 and checkpoint with forkhead and RING finger domain protein (Chfr).

reach
In such experiments, USP7 CI interacted more strongly with endogenous Claspin than did WT USP7 (XREF_FIG), which is consistent with a substrate trapping mechanism in which an inability of inactive USP7 to deubiquitylate Claspin would manifest as a prolonged binding and thus a tighter interaction.

ubibrowser
Review
USP7 deubiquitinates PCNA. 5 / 5
| 4

reach
USP7 can deubiquitinate PCNA alongside a related DUB, USP1.
| PMC

ubibrowser
Review

reach
Kashiwaba et al. have additionally shown that USP7 can deubiquitylate PCNA, but this is not coupled to DNA replication and likely plays a role in DNA repair.

reach
Surprisingly, USP7 also deubiquitylates PCNA.

reach
Cell-cycle-synchronization analyses revealed that USP7 suppression increased H2O2 induced PCNA ubiquitination throughout interphase, whereas USP1 suppression specifically increased ubiquitination in S-phase cells.
USP7 deubiquitinates CHFR. 5 / 5
| 4

ubibrowser
Review

reach
Thus, we examined whether USP7 can mediate the deubiquitination of Chfr in vivo.

reach
These results demonstrate that USP7 preferentially functions in deubiquitination of Chfr, and prevents autoubiquitination mediated degradation of Chfr.The present study has demonstrated that Chfr bind[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

reach
Deubiquitination of Chfr, a checkpoint protein, by USP7 and HAUSP regulates its stability and activity.

reach
Ubiquitin specific protease, USP7 and HAUSP deubiquitinates CHFR and prevents its degradation, resulting in the increased stability [9].
USP7 deubiquitinates DAXX. 5 / 5
| 4

reach
Furthermore, Hausp de-ubiquitinated Daxx and regulated stability of endogenous Daxx.

ubibrowser
Review

reach
Similar to what has been reported with Mdm2 and p53, Hausp strongly de-ubiquitinated Daxx (XREF_FIG).

reach
The strong interaction between Daxx and Hausp, and that Daxx is ubiquitinated by Mdm2 and other E3s suggest that Hausp might de-ubiquitinate Daxx.

reach
Daxx is deubiquitinated by Hausp.
USP7 deubiquitinates IKBKG. 5 / 5
| 4

reach
Cytoplasmic USP7 binds to and deubiquitinates TRAF6 and IKKgamma, thus terminating TLR mediated NF-kappaB and JNK activation.

ubibrowser
Review

reach
The aforementioned data demonstrated that both HSCARG and USP7 inhibit NEMO polyubiquitination, and suppression of NEMO polyubiquitination by HSCARG is dependent on USP7.

reach
To determine whether USP7 deubiquitinated NEMO polyubiquitination, we examined and compared the levels of NEMO polyubiquitination in HEK 293T cells with or without ectopic USP7.

reach
Inhibition of NEMO polyubiquitination by USP7 suggested that USP7 probably inhibited cytokine induced NF-kappaB activation.
USP7 deubiquitinates RB1. 4 / 4
| 3

reach
HAUSP deubiquitinates Rb in vivo and in vitro, leading to an increased cell population in the G1 phase.

reach
HAUSP deubiquitinates Rb.

ubibrowser
Review

reach
In addition to stabilization of MDM2 by HAUSP, it might be possible that HAUSP reverses Rb ubiquitination by MDM2 in normal cells but is overwhelmed by abundant MDM2 in the case of tumor tissues or cancer cells.
USP7 deubiquitinates MYCN. 4 / 4
| 3

reach
HAUSP deubiquitinates and stabilizes N-Myc in neuroblastoma.

reach
The ubiquitin specific peptidase HAUSP (also known as USP7) binds to and deubiquitinates MYCN leading to its stabilization (XREF_FIG).

ubibrowser
HAUSP deubiquitinates and stabilizes N-Myc in neuroblastoma

reach
HAUSP deubiquitinates and stabilizes N-Myc in neuroblastoma.
USP7 deubiquitinates RAD18. 4 / 4
| 3

ubibrowser
?Here, we identify the de-ubiquitylating enzyme USP7 as a critical regulator of Rad18 protein levels. Loss of USP7 destabilizes Rad18 and compromises UV-induced PCNA mono-ubiquitylation and Pol 畏 recruitment to stalled replication forks.?

reach
In response to replication stress, USP7 also deubiquitylates and stabilizes both Rad18 (so that it can monoubiquitylate PCNA) and the TLS polymerase, polymerase eta (POL-eta), and this facilitates the bypass of lesions through the error-prone TLS pathway.

reach
USP7 deubiquitinates RAD18 which leads to stabilisation and up-regulation of PCNA ubiquitination.
| PMC

reach
This is likely concomitant with Pol eta deubiquitination by USP7 and PIAS1 and Rad18 dependent SUMOylation [XREF_BIBR, XREF_BIBR] (XREF_FIG A).
USP7 deubiquitinates CD274. 4 / 4
| 4

reach
Similarly, treatment of MFC cells with mUSP7-sgRNA-lentivirus or Almac4 also led to similar results which further confirm the results derived from XREF_FIG G and H. All these results indicate that USP7 interacts with PD-L1 and deubiquitinates PD-L1 to promote the stability of PD-L1.

reach
Results in XREF_FIG E suggest that PD-L1 was strongly ubiquitinated (lane 2, XREF_FIG E) in the presence of MG132 but without HA-USP7, while HA-USP7 abolished PD-L1 ubiquitination (lane3, XREF_FIG E).

reach
In the current study, we show that USP7 deubiquitinates PD-L1 to cause cancer immune resistance to promote cancer growth.

reach
Then, to further verify that USP7 can deubiquitinate PD-L1, Flag-PD-L1 was co-transfected with HA-His-Ub in the presence of HA-USP7 or not in HEK293cells.
USP7 deubiquitinates CRYL1. 4 / 4
| 4

reach
These results demonstrate that USP7 deubiquitinates CRY proteins.

reach
USP7 deubiquitinates CRY proteins.

reach
Fbxl3 knockdown in HEK293T/17 cells did not abrogate USP7 dependent stabilizing effect on CRY2 (XREF_FIG), suggesting that USP7 deubiquitinates CRY protein that was ubiquitinated by multiple E3 ligases.

reach
Given that MAGEL2 interacts with USP7, and that CRY proteins are deubiquitinated and stabilized by USP7, we tested the effect of MAGEL2 and USP7 on the ubiquitination of CRY1.
Modified USP7 leads to the deubiquitination of REST. 4 / 4
| 4

reach
Moreover, deubiquitination assay demonstrated that expression of Wt-HAUSP but not the Mt-HAUSP attenuated the REST ubiquitination induced by B5 shHAUSP (XREF_FIG), showing that Wt-HAUSP functioned through deubiquitination to stabilize REST and rescued the differentiation phenotype induced by knockdown of endogenous HAUSP.

reach
Consistently, expression of HAUSP reduced REST poly-ubiquitination (XREF_SUPPLEMENTARY, lanes 2, 1), and overexpression of beta-TrCP increased REST ubiquitination (XREF_SUPPLEMENTARY, lanes 3, 2).

reach
Ectopic expression of Wt-HAUSP but not the Mt-HAUSP decreased REST ubiquitination and increased REST protein levels (XREF_FIG; XREF_SUPPLEMENTARY).

reach
Importantly, overexpression of HAUSP with beta-TrCP together abolished the increased REST ubiquitination induced by beta-TrCP overexpression (XREF_SUPPLEMENTARY, lanes 4, 3).
USP7 deubiquitinates E3_Ub_ligase. 4 / 4
| 4

reach
USP7 deubiquitinates the E3 ubiquitin ligase NEDD4L, which mediates the degradation of SMAD2.

reach
USP7 deubiquitinates several tumour suppressors (p53, PTEN, FOXO and claspin) and E3 ligases (MDM2, Mule and viral proteins ICP0) and therefore regulates important signalling pathways that are involved in tumorigenesis XREF_BIBR XREF_BIBR.

reach
Interestingly, USP7 can deubiquitinate both p53 and its negative regulator HDM2, an E3 ubiquitin ligase responsible for polyubiquitination and subsequent degradation of p53.

reach
XREF_BIBR - XREF_BIBR USP7 deubiquitinates and stabilizes not only p53, but also Mdm2, the primary E3 ubiquitin ligase of p53 XREF_BIBR, XREF_BIBR Given that both p53 and Mdm2 are known regulators of the steady-level of Poleta, we speculated that changes in cellular USP7 levels may also modulate Poleta level.
USP7 deubiquitinates XPC. 4 / 4
| 3

reach
Inhibition of USP7 increases XPC ubiquitination level, and without USP7, cells have decreased efficiency in repairing UV lesions [XREF_BIBR, XREF_BIBR].

reach
Other proteins involved in the stabilization of XPC might be the deubiquitylating enzymes OTUD4 and USP7, which were shown to deubiquitylate XPC upon UV induced DNA damage XREF_BIBR XREF_BIBR.

reach
Specifically, UV induced XPC proteasomal degradation occurs without protection by USP7 which deubiquitinates XPC.

ubibrowser
Review
USP7 deubiquitinates NEK2. 4 / 4
| 4

reach
USP7 interacts with and deubiquitinates NEK2.

reach
Next we examined whether the increase in NEK2 protein levels was dependent upon the deubiquitinating enzymatic activity of USP7, and found that ectopic expression of USP7 decreased NEK2 ubiquitination.

reach
We therefore examined whether USP7 deubiquitinated NEK2 and affected its function in PAs, and confirmed a specific interaction between USP7 and NEK2 in transiently transfected HEK293T cells using co-immunoprecipitation.

reach
Studies have shown that USP7 deubiquitinates NEK2 and affects its stability XREF_BIBR.
USP7 leads to the deubiquitination of PHF8. 4 / 4
| 3

reach
Specifically, we demonstrated that USP7 promotes deubiquitination and stabilization of PHF8, leading to the upregulation of a group of genes, including cyclin A2, that are critical for cell growth and proliferation.

reach
For instance, USP7 promotes the deubiquitination and stabilization of PHF8 [13].

reach
showed that USP7 promotes deubiquitination and stabilization of PHF8 in breast cancer MCF7 cells, accounting for a mechanism underlying PHF8 deregulation.

ubibrowser
Here, we report that PHF8 physically associates with the deubiquitinase USP7.
USP7 deubiquitinates NLRP3. 3 / 3
| 3

reach
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].
| PMC

reach
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].

reach
Therefore, H 2 O 2 treatment increases the protein level of NLRP3 and pro-caspase-1 due to the induction of USP7 dependent deubiquitination of NLRP3 and/or activation of NOX4/ROS/NF-kappaB signaling that is capable of DNA binding.
USP7 deubiquitinates ECT2. 3 / 3
| 3

reach
USP7 in turn, deubiquitinates and stabilizes ECT2, resulting in a feedforward regulatory circuit that ultimately sustains the expression of oncogenic protein MDM2.

reach
Given that ECT2 is an ubiquitinated protein XREF_BIBR, XREF_BIBR and USP7 promotes the stabilization of ECT2, we next asked the question whether USP7 functions to deubiquitinate ECT2.

reach
Specifically, we uncovered that ECT2 and USP7 form a positive feedback loop, in which ECT2 promotes USP7 intermolecular self association, -deubiquitination and -stabilization, and reciprocally, USP7 deubiquitinates and stabilizes ECT2.
USP7 deubiquitinates UHRF1. 3 / 3
| 2

ubibrowser
Review

reach
Indeed, USP7 mediates deubiquitylation of UHRF1, preventing its proteasomal degradation.

reach
Both UHRF1 and DNMT1 are deubiquitinated and stabilized by USP7 [XREF_BIBR, XREF_BIBR], while UHRF1 is the negative regulator of DNMT1 [XREF_BIBR].
USP7 deubiquitinates SUV39H1. 3 / 3
| 3

reach
Collectively, these results indicate that shared physical interactions of USP7 and SUV39H1 with MDM2 are required either for USP7 to deubiquitinate SUV39H1 or for MDM2 to ubiquitinate SUV39H1, both re[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

reach
Collectively, these results indicate that shared physical interactions of USP7 and SUV39H1 with MDM2 are required for either for USP7 to deubiquitinate SUV39H1 or for MDM2 to ubiquitinate SUV39H1; both resulting in enhanced SUV39H1 stability.

reach
In the absence of p53, USP7 deubiquitinates SUV39H1 providing protection from MDM2 ubiquitination and USP7, MDM2 and SUV39H1 form a DNA independent trimeric complex.35Finally, the role of US7 in regulation of epigenetic regulators is evidenced by the interaction of USP7 with LSD1.
| PMC
USP7 deubiquitinates MARCHF7. 3 / 3
| 2

ubibrowser
It has been proposed that USP7 may reverse self-ubiquitination of the Ub E3 ligase MARCH7, thus stabilizing MARCH7 which has been known to regulate the expression levels of E-cadherin and β-catenin

reach
Exogenous expression and short interfering RNA depletion experiments demonstrate that MARCH7 can be stabilized by both USP9X and USP7, which deubiquitylate MARCH7 in the cytosol and nucleus, respectively.

reach
It has been proposed that USP7 may reverse self ubiquitination of the Ub E3 ligase MARCH7, thus stabilizing MARCH7 which has been known to regulate the expression levels of E-cadherin and beta-catenin.
USP7 deubiquitinates NOX4. 3 / 3
| 3

reach
USP7 inhibited NOX4 ubiquitination for degradation which leads to elevated ROS production.

reach
In summary, this study showed that USP7 deubiquitinates NOX4 to stabilize it, which leads to elevated ROS production.

reach
This study showed that USP7 interacted with and deubiquitinated NOX4, and the inhibition of ROS production or administration of NOX4 inhibitor significantly inhibited oeUSP7 induced pro OA effects such as enhanced pyroptosis, elevated ROS level, increased IL-1beta and IL-18 levels, and overexpression of NLRP3, GSDMD-N, active caspase-1, and pro-caspase-1.
USP7 deubiquitinates AR. 3 / 3
| 2

ubibrowser
We showed that USP7 associates with AR in an androgen-dependent manner and mediates AR deubiquitination.

reach
USP7 deubiquitinates full-length AR, but not AR-V7, in prostate cancer cells, which suggests that the LBD domain of AR may be critical for USP7 recruitment.

reach
USP7 mediates AR deubiquitination and associates with AR, in an androgen dependent manner, driving the transcription of target genes and promoting prostate cells growth [XREF_BIBR].
USP7 deubiquitinates TRAF6. 3 / 3
| 3

reach
USP15 negatively regulates NFjB activation by deubiquitinating IjB (Harhaj and Dixit 2011) , while USP7 decreases NFkB signalling by deubiquitinating TRAF6 and IKK (Nanduri et al. 2013 ).

reach
While in vitro interactions of USP7 NTD with TRAFs 1 to 6, intracellular USP7 binding to TRAFs 4 and 6, and USP7 deubiquitination of TRAF6 have been reported, biological targeting and deubiquitination of the TRAFs by USP7 have generally not been assessed.

reach
Cytoplasmic USP7 binds to and deubiquitinates TRAF6 and IKKgamma, thus terminating TLR mediated NF-kappaB and JNK activation.
USP7 deubiquitinates EZH2. 3 / 3
| 1 2

reach
USP7 deubiquitinates and stabilizes EZH2 in prostate cancer cells.

reach
We report here that the PRC2 complex is physically associated with ubiquitin specific protease USP7 in cancer cells where USP7 acts to deubiquitinate and stabilize EZH2.

trips
USP7 deubiquitinates and stabilizes EZH2 in prostate cancer cells.
USP7 deubiquitinates FOXO. 3 / 3
| 3

reach
This process may be reversed by the deubiquitination of FOXO proteins mediated by HAUSP and USP7.

reach
Deubiquitination of Foxo is mediated by the deubiquitinating enzyme USP7.

reach
Deubiquitination of FOXO requires the deubiquitinating enzyme USP7 and HAUSP (herpesvirus associated ubiquitin specific protease), which interacts with and deubiquitinates FOXO in response to oxidative stress.
USP7 deubiquitinates CDC25A. 3 / 3
| 3

reach
These data support that BRE upregulation facilitates deubiquitylation of CDC25A in the presence of DNA damage by USP7.

reach
USP7 also deubiquitinates the cell cycle checkpoint CDC25A upon DNA damage in the BRCA deficient cells and contributes to cell survival despite the loss of BRCA mediated genome integrity.

reach
Furthermore, in a co-immunoprecipitation assay, we found that HAUSP interacts with and deubiquitinates Cdc25A both exogenously and endogenously.
USP7 leads to the deubiquitination of ARMC5. 3 / 3
| 3

reach
Silencing of USP7 enhanced ARMC5 ubiquitination and accelerated cell cycle G1/S, subsequently promoted RCC cell proliferation.

reach
Conversely, overexpression of USP7, but not its catalytically mutant, reversed ARMC5 ubiquitination levels.

reach
Silencing of USP7 decreased ARMC5 levels, accompanied by increasing ARMC5 polyubiquitination, whereas overexpression of USP7 but not its mutants increased ARMC5 levels and reversed ARMC5 polyubiquitination.
USP7 deubiquitinates RIPK1. 3 / 3
| 2

reach
Subsequently, USP7 deubiquitinates the receptor interacting protein 1 (RIP1), resulting in positive regulation of TNF-alpha-induced apoptosis.

ubibrowser
Review

reach
USP7 also deubiquitinates RIP1 following activation by the TRIM27 E3 ligase resulting in apoptosis.
USP7 deubiquitinates CRY1. 3 / 3
| 2

ubibrowser
We found that ubiquitin-specific protease 7 (USP7 also known as HAUSP) associates with CRY1 and CRY2 and stabilizes CRYs through deubiquitination.

reach
Recombinant Hausp can deubiquitinate Cry1 in vitro (XREF_FIG).

reach
We then tested whether USP7 can deubiquitinate CRY1.
USP7 leads to the deubiquitination of KDM1A. 3 / 3
| 2

ubibrowser
Review

reach
USP7 inhibited LSD1 ubiquitination and stabilized LSD1 in A172 and T98G cells.

reach
Furthermore, USP7 inhibits LSD1 ubiquitination and stabilizes LSD1in glioma [XREF_BIBR].
Modified USP7 leads to the deubiquitination of FOXP3. 3 / 3
| 3

reach
Ectopic expression of USP7 specifically decreased Foxp3 polyubiquitination, resulting in increased Foxp3 expression.

reach
Ectopic expression of USP7 specifically decreased Foxp3 polyubiquitination, resulting in increased Foxp3 protein expression.

reach
Ectopic expression of USP7 decreased Foxp3 polyubiquitination and increased Foxp3 expression.
Modified USP7 leads to the deubiquitination of TP53. 3 / 3
| 3

reach
There also seems to be a delicate balance between these proteins, as a modest reduction of HAUSP levels prevents p53 deubiquitination but complete ablation of HAUSP causes robust p53 stabilization.

reach
As shown in XREF_FIG, Mdm2 induced the ubiquitination of p53; however, p53 ubiquitination was significantly diminished by coexpression of USP10 or HAUSP.

reach
The expression of USP7/HAUSP prevents p53 ubiquitination from Mdm2 as a p53-specific E3 ligase and increases the p53 protein stability [25].
| PMC
USP7 deubiquitinates PRC1. 3 / 3
| 2

reach
Lastly, USP7 and USP11 deubiquitinate PRC1, a protein found to contribute to cancer stemness [XREF_BIBR - XREF_BIBR].

reach
In some cancer types, PRC1 can be deubiquitinated by USP7, USP11 and USP26 [XREF_BIBR, XREF_BIBR].

ubibrowser
Review
USP7 leads to the deubiquitination of AXIN1. 2 / 2
| 1

ubibrowser
USP7 directly interacts with Axin through its TRAF domain, and promotes deubiquitination and stabilization of Axin.

reach
Ubiquitin carboxyl-terminal hydrolase 7 (USP7), a potent negative regulator of Wnt and beta-catenin signaling, promotes the deubiquitination and stabilization of AXIN by interacting with AXIN through its TRAF domain [XREF_BIBR].
USP7 deubiquitinates GLI1. 2 / 2
| 1

reach
HAUSP Deubiquitinates Gli and Promotes Hh Signaling Activity in Mammalian Systems.

ubibrowser
Deubiquitination of Ci/Gli by Usp7/HAUSP regulates Hedgehog Signaling
USP7 deubiquitinates TP53 on lysine. 2 / 2
2 |

biopax:reactome
No evidence text available

biopax:pid
No evidence text available
USP7 deubiquitinates NEDD4L. 2 / 2
| 1

ubibrowser
USP7 deubiquitinates the E3 ubiquitin ligase NEDD4L, which mediates the degradation of SMAD2.

reach
USP7 deubiquitinates the E3 ubiquitin ligase NEDD4L, which mediates the degradation of SMAD2.
USP7 deubiquitinates FBP1. 2 / 2
| 2

reach
Moreover, we revealed that ubiquitin carboxyl-terminal hydrolase 7 (USP7) binds to and induces the deubiquitination of FBP1, which prevented FBP1 from translocating to the nucleus.

reach
Deubiquitination of FBP1 by USP7 blocks FBP1-DNMT1 interaction and decreases the sensitivity of pancreatic cancer cells to PARP inhibitors.
USP7 deubiquitinates NOTCH1. 2 / 2
| 2

reach
USP7 deubiquitinated NOTCH1 in vivo and in vitro, whereas knockdown of USP7 increased the ubiquitination of NOTCH1.

reach
USP7 deubiquitinates and stabilizes NOTCH1 in T-cell acute lymphoblastic leukemia.
USP7 deubiquitinates IKK_complex. 2 / 2
| 2

reach
USP15 negatively regulates NFjB activation by deubiquitinating IjB (Harhaj and Dixit 2011) , while USP7 decreases NFkB signalling by deubiquitinating TRAF6 and IKK (Nanduri et al. 2013 ).

reach
USP15 negatively regulates NFκB activation by deubiquitinating IκB (Harhaj and Dixit 2011), while USP7 decreases NFkB signalling by deubiquitinating TRAF6 and IKK (Nanduri et al. 2013).
USP7 deubiquitinates USP7. 2 / 2
| 2

reach
In addition, utilizing the UbiTest analysis we demonstrate that inhibition of USP7 increases polyubiquitination of Foxp3, Tip60 and USP7.

reach
However, HAUSP also deubiquitinates MDM2 and reduction of HAUSP levels, either by RNA interference or by gene deletion, produces a complex phenotype [XREF_BIBR - XREF_BIBR].
USP7 deubiquitinates Wnt. 2 / 2
| 2

reach
31 HAUSP in complex with RNF220 deubiquitinates beta-catenin-enhancing canonical Wnt signaling.

reach
Collectively, we concluded that the USP7 mediated beta-catenin deubiquitination and Wnt activation are specific to CRCs carrying APC mutations and are p53 independent.
USP7 leads to the deubiquitination of UBE2E1. 2 / 2
| 1

reach
We show that USP7 attenuates UbE2E1 mediated ubiquitination, an effect that requires the N-terminal ASTS sequence of UbE2E1 as well as the catalytic activity of USP7.

ubibrowser
UbE2E1/UbcH6 is an E2 ubiquitin-conjugating enzyme that is regulated by USP7.
USP7 deubiquitinates Histone_H3. 2 / 2
| 2

reach
USP7 stabilizes several other histone associated proteins including acetyltransferase TIP60, demethylase PHF8, methyltransferase MLL5, lysine specific demethylase 1 (LSD1 and KDM1), and directly deubiquitinates histone H3.

reach
Our results thus suggest that histone H3 deubiquitylation by Usp7 is an important step in the maintenance of DNA methylation.
USP7 leads to the deubiquitination of Cyclin on A2. 2 / 2
| 2

reach
The exosomal circ-DB internalized by HCC cells can be used as a molecular sponge to absorb miR-34a endogenously, thereby deinhibiting the downstream target USP7, which inhibits the ubiquitination of cyclin A2 protein to maintain its stability.

reach
USP7 mediates the deubiquitination of cyclin A2 in HCC.
USP7 leads to the deubiquitination of BMI1. 2 / 2
| 1

reach
Also, a recent study suggested that USP7 attenuates the ubiquitination of BMI1, its homologue Mel-18, and RING1A, which are components of the PRC1 complex [15].

ubibrowser
Review
USP7 leads to the deubiquitination of tat. 2 / 2
| 2

reach
USP7 has also been shown to promote HIV-1 infection by deubiquitylating and stabilizing the HIV-1 Tat protein 73.

reach
Finally, besides its role in infections mediated by Herpesviruses, USP7 also promotes adenoviral replication via interaction with viral multifunctional protein E1B-55K and enhances HIV viral production by deubiquitinating its Tat protein.
USP7 leads to the deubiquitination of PML. 2 / 2
| 1

ubibrowser
Review

reach
Here we showed that USP7 can also function independently from its deubiquitylating activity to negatively regulate the levels of PML proteins and the formation of PML-NBs, by inducing the polyubiquitylation of PML.
USP7 deubiquitinates ubiquitinated TP53. 2 / 2
| 2

reach
HAUSP specifically deubiquitinates the ubiquitinated p53 protein both in vitro and in vivo, and the expression of HAUSP was found to stabilize p53 in vivo and to promote p53 dependent cell growth arre[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

reach
Single- or double ubiquitinated p53 are deubiquitinated by a protein called HAUSP XREF_BIBR.
USP7 deubiquitinates TRIM27. 2 / 2
| 1

ubibrowser
Our findings suggest that USP7 acts as a negative regulator in antiviral signaling by stabilizing TRIM27 and promoting the degradation of TBK1.

reach
First, USP7 deubiquitinates TRIM27 to prevent its own auto-degradation and thus stabilizes the complex.
USP7 deubiquitinates washc1. 2 / 2
| 2

reach
Taken together, these results suggest that USP7 limits overproduction of endosomal F-actin by WASH through its ability to deubiquitinate WASH and that precise endosomal F-actin levels are critical for[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

reach
Taken together, these results suggest that USP7 limits overproduction of endosomal F-actin by WASH through its ability to deubiquitinate WASH (XREF_FIG) and that precise endosomal F-actin levels are critical for proper endosomal protein recycling.
USP7 deubiquitinates EDNRA. 2 / 2
| 2

reach
Pol eta is also deubiquitinated by USP7, leading to the recruitment of PCNA to stalled replication forks and PCNA 's ubiquitination by Rad 6 and Rad18 [XREF_BIBR].

reach
This is likely concomitant with Pol eta deubiquitination by USP7 and PIAS1 and Rad18 dependent SUMOylation [XREF_BIBR, XREF_BIBR] (XREF_FIG A).
USP7 deubiquitinates SVIL. 2 / 2
| 1 1

reach
USP7 binds directly to the supervillin N terminus and can deubiquitinate and stabilize supervillin.

trips
USP7 binds directly to the supervillin N terminus and can deubiquitinate and stabilize supervillin.
USP7 deubiquitinates CRY2. 2 / 2
| 1

reach
Here, we demonstrated that, even in the absence of any DNA damage inducible stimuli, not only CRY1 but also CRY2 binds to USP7 and is deubiquitinated by USP7 (Figs XREF_FIG and XREF_FIG).

ubibrowser
We found that ubiquitin-specific protease 7 (USP7 also known as HAUSP) associates with CRY1 and CRY2 and stabilizes CRYs through deubiquitination.
USP7 deubiquitinates RELA. 2 / 2
| 1

reach
However, USP7 deubiquitinates the NF-kappaB p65 subunit, which is an important regulator of inflammation, but the USP7 inhibitor targets all the substrates of USP7, not only p65.

ubibrowser
Review
USP7 leads to the deubiquitination of FOXO4. 2 / 2
| 1

ubibrowser
Review

reach
USP7 negatively regulates FOXO by antagonizing FOXO4 monoubiquitylation and activity without affecting protein stability.
USP7 leads to the deubiquitination of NFE2L1. 1 / 1
| 1

reach
In contrast, knockdown or pharmacologic inhibition of USP7 dramatically increased ubiquitination of TCF11 and Nrf1a, and reduction of their steady state levels.
USP7 deubiquitinates POLH. 1 / 1
|

ubibrowser
USP7 directly serves as a specific DUB for Poleta
USP7 deubiquitinates RNF168. 1 / 1
|

ubibrowser
Review
Modified USP7 leads to the deubiquitination of CTNNB1. 1 / 1
| 1

reach
Expression of WT USP7 robustly suppressed beta-catenin ubiquitination, as demonstrated by mobility shift, while the C223A mutant expression failed to execute its function (XREF_FIG H and XREF_SUPPLEMENTARY G).
USP7 deubiquitinates FUS. 1 / 1
| 1

reach
In response to replication stress, USP7 also deubiquitylates and stabilizes both Rad18 (so that it can monoubiquitylate PCNA) and the TLS polymerase, polymerase eta (POL-eta), and this facilitates the bypass of lesions through the error-prone TLS pathway.
USP7 deubiquitinates MAFA. 1 / 1
| 1

reach
Stability of MAF proteins in MM is further regulated by the deubiquitinases ubiquitin specific peptidase 5 (USP5), which prevents degradation of c-MAF and MAFB [XREF_BIBR], and USP7, which can deubiquitinate c-MAF, MAFA and MAFB [XREF_BIBR].
Modified USP7 leads to the deubiquitination of DNMT1. 1 / 1
| 1

reach
Second, DNMT1 ubiquitination was increased in the HAUSP knockout cells (XREF_FIG), whereas overexpression of HAUSP led to deubiquitination of DNMT1 (XREF_FIG).
USP7 deubiquitinates IRS2. 1 / 1
|

ubibrowser
Review
USP7 leads to the deubiquitination of mutated DNMT1. 1 / 1
| 1

reach
Experimental controls further showed that (i) a HAUSP C223S (active site) mutant could not remove ubiquitin moieties from DNMT1 (XREF_FIG), and (ii) overexpressed HAUSP failed to deubiquitinate a DNMT1 mutant lacking the HAUSP interaction domain (DNMT1Delta) (XREF_SUPPLEMENTARY).
USP7 leads to the deubiquitination of RING1. 1 / 1
| 1

reach
His ubiquitin pull-down analysis showed that HSCARG and USP7 inhibited RING1 ubiquitination in a synergy manner.
USP7 leads to the deubiquitination of ARF4. 1 / 1
| 1

reach
USP7 inhibition induces apoptosis in glioblastoma by enhancing ubiquitination of ARF4.
USP7 deubiquitinates HIF1. 1 / 1
| 1

reach
The accumulative USP7 resulted in deubiquitylation and stabilization of HIF-1α, thereby facilitating resistance to oxaliplatin.
USP7 deubiquitinates FOXP3. 1 / 1
| 1

reach
56 In other words, USP7 deubiquitinates Foxp3, increasing Foxp3 protein levels and subsequently up-regulating Treg cells.A knockdown of USP7 expression in the Treg cells leads to a decrease in the Foxp3 protein levels reducing the suppression of the Treg-cell in vitro and vivo.45 USP7 inhibitors can affect the tumour growth limitation in immunocompetent mice and may have a key role in future cancer immunotherapies.56USP7 has also been implicated in regulation of the inflammasome.
| PMC
USP7 deubiquitinates FOXO3. 1 / 1
|

ubibrowser
USP7 deubiquitinates checkpoint with forkhead and RING finger domains protein (Chfr), which in turn ubiquitinates histone deacetylase 1 (HDAC1), leading to upregulation of p21Cip1/Waf1?and induction of G1 arrest
USP7 deubiquitinates CREB3. 1 / 1
| 1

reach
Similarly, USP7 deubiquitination of FOXO4 's monoubiquitinated, transcriptionally active form excludes it from the nucleus, eliminating its activity [XREF_BIBR].
USP7 deubiquitinates ALKBH3. 1 / 1
| 1

reach
Instead, it seemed to act as a scaffold protein, recruiting two further DUBs, USP7 and USP9x, which then de-ubiquitylated ALKBH3.
USP7 deubiquitinates PCGF2. 1 / 1
| 1

reach
Nevertheless, MEL18 and BMI were deubiquitylated by USP7 and USP11, two chromatin bound components of polycomb and repressive complex 1 complex components that influence the transcriptional regulation of p16INK4a [XREF_BIBR].
Modified USP7 leads to the deubiquitination of CRY1. 1 / 1
| 1

reach
CRY1 is ubiquitinated in this assay (XREF_FIG, CRY1 ub smear in lane 2), and co-expression of USP7 reduced CRY1 ubiquitination (ubiquitin smear in lane 3 compared to lane 2).
USP7 deubiquitinates ubiquitinated HIF1A. 1 / 1
| 1

reach
In vitro deubiquitination assays using purified polyubiquitinated HIF-1alpha and Flag-HAUSP (wild-type versus K443R mutant) showed that the wild-type HAUSP, but not the K443R mutant, significantly deubiquitinated the polyubiquitinated HIF-1alpha species (XREF_FIG).
USP7 deubiquitinates ubiquitinated HSD17B8. 1 / 1
| 1

reach
USP7 also deubiquitinates autoubiquitinated RING2 ligase of the polycomb complex and RING2 that has been marked for degradation by the E6AP ligase.
USP7 deubiquitinates TRRAP. 1 / 1
| 1

trips
HAUSP regulates c-MYC expression via de-ubiquitination of TRRAP.
Modified USP7 leads to the deubiquitination of SPRTN. 1 / 1
| 1

reach
Furthermore, deubiquitylation of SPRTN induced by overexpression of USP7 WT, but not of catalytically inactive USP7 CS, leads to reduced formation of autocatalytic SPRTN fragments.
USP7 deubiquitinates TP53BP1. 1 / 1
|

ubibrowser
53BP1 depletion induces mitotic defects such as disorientation of spindle poles attributed to extra centrosomes or mispositioning of centrosomes, leading to phenotypes similar to those in USP7-deficient cells.
Modified USP7 leads to the deubiquitination of TBK1. 1 / 1
| 1

reach
Overexpression of USP7 promoted the ubiquitination and degradation of TBK1 through promoting the stability of TRIM27.
USP7 deubiquitinates H2BC10. 1 / 1
|

ubibrowser
Review
USP7 deubiquitinates MYC. 1 / 1
|

ubibrowser
Most importantly, we are able to demonstrate that USP7 deubiquitinates and thereby stabilizes c-Myc and that this function is required to maintain neural stem cell fate.
USP7 leads to the deubiquitination of ICP0. 1 / 1
| 1

reach
47 Similarly, HAUSP blocks ICP0 autoubiquitination 48 and enhances ICP0 protein stability.
USP7 deubiquitinates RAE1. 1 / 1
| 1

reach
USP7, which co-IPs with USP11 and can co-IP USP11, RAE1, PAM and SPRYD3 (XREF_SUPPLEMENTARY), efficiently deubiquitinated SPRYD3, whilst RAE1 is only weakly deubiquitinated by USP7 (XREF_FIG).
USP7 deubiquitinates FOXO1. 1 / 1
|

ubibrowser
Review
USP7 deubiquitinates YAP1. 1 / 1
|

ubibrowser
Furthermore, the mammalian homolog of Usp7, HAUSP plays a conserved role in regulating Hippo pathway by modulating Yap ubiquitination and degradation.
USP7 deubiquitinates DNMT3B. 1 / 1
| 1

reach
FA decreased the ubiquitination of DNMT1 (p = 0.0753), DNMT3A (p = 0.0008) and DNMT3B (p < 0.0001) by decreasing UHRF1 (p < 0.0001) and USP7 (p < 0.0001).
Modified USP7 leads to the deubiquitination of GMPS. 1 / 1
| 1

reach
Of note, USP7 overexpression leads to GMPS deubiquitylation and nuclear retention.
USP7 deubiquitinates NFKB1. 1 / 1
|

ubibrowser
Review
Modified USP7 leads to the deubiquitination of NCL. 1 / 1
| 1

reach
Overexpression of wild-type HAUSP, but not a catalytic mutant (C223S) decreased nucleolin ubiquitination (XREF_FIG, lane 3).
USP7 deubiquitinates RNF220. 1 / 1
| 1

reach
Specifically, USP7 binds the N-terminus of β-catenin when the APC losses CID confirming the essential role of USP7 in the activation of Wnt signalling and cell survival in colorectal cancers.13 Ma et al showed that the USP7/RNF220 complex activates the Wnt pathway while knockdown of USP7 using a small interfering RNA (siRNA) strategy, reduces the expression of Wnt.18 Conversely, a recent study proposed that USP7 deubiquitinates β-catenin and RNF220 independently and works as a tumour-specific condition when APC is mutated.
| PMC
USP7 leads to the deubiquitination of NCL. 1 / 1
| 1

reach
Therefore, we examined the pattern of polyubiquitination and deubiquitination of nucleolin following HAUSP overexpression (XREF_FIG).
USP7 deubiquitinates SIRT7. 1 / 1
|

ubibrowser
Ubiquitin-specific peptidase 7 (USP7)-mediated deubiquitination of the histone deacetylase SIRT7 regulates gluconeogenesis
USP7 deubiquitinates PTEN ubiquitinated on K13 on K289. 1 / 1
1 |

biopax:reactome
No evidence text available
USP7 deubiquitinates RARA. 1 / 1
|

ubibrowser
overexpression or depletion of USP37 caused an increase or decrease of PLZF/RARA protein half-life, correlating with down- or upregulation of PLZF/RARA poly-ubiquitination, respectively. By PLZF/RARA-transduced primary mouse hematopoietic progenitor cells, we demonstrated that Usp37 knockdown alleviated PLZF/RARA-mediated target gene suppression and cell transformation potential
USP7 deubiquitinates HLTF. 1 / 1
|

ubibrowser
Review
USP7 deubiquitinates IRS1. 1 / 1
|

ubibrowser
Review
USP7 deubiquitinates FOXO4 on lysine. 1 / 1
1 |

biopax:pid
No evidence text available
USP7 deubiquitinates HSD17B8. 1 / 1
| 1

reach
USP7 also deubiquitinates autoubiquitinated RING2 ligase of the polycomb complex and RING2 that has been marked for degradation by the E6AP ligase.
USP7 deubiquitinates MAF. 1 / 1
| 1

reach
Stability of MAF proteins in MM is further regulated by the deubiquitinases ubiquitin specific peptidase 5 (USP5), which prevents degradation of c-MAF and MAFB [XREF_BIBR], and USP7, which can deubiquitinate c-MAF, MAFA and MAFB [XREF_BIBR].

reach
39 USP7 also deubiquitinates RNA transcriptional activator associated ubiquitin ligase and prevents it from self-ubiquitination-mediated degradation.
USP7 deubiquitinates UVSSA. 1 / 1
|

ubibrowser
The central region of UVSSA, which contains the tumor necrosis factor receptor-associated factor (TRAF)-binding motif, is required for the interaction with the N-terminal TRAF domain of USP7. Here, we showed that UVSSA is mono-ubiquitinated in?vitro and identified a lysine residue (Lys414?) in UVSSA as the target of ubiquitination. The deubiquitination activity of USP7 was inhibited by the ubiquitin-conjugating enzyme UbcH6. Lys414?was also modified by poly-ubiquitin chains in?vivo.?
USP7 deubiquitinates AURKA. 1 / 1
|

ubibrowser
Review
USP7 deubiquitinates MAFB. 1 / 1
| 1

reach
Stability of MAF proteins in MM is further regulated by the deubiquitinases ubiquitin specific peptidase 5 (USP5), which prevents degradation of c-MAF and MAFB [XREF_BIBR], and USP7, which can deubiquitinate c-MAF, MAFA and MAFB [XREF_BIBR].
Modified USP7 leads to the deubiquitination of FOXP3. 1 / 1
| 1

reach
As expected, USP44 or USP7 expression alone reduced ubiquitination of FOXP3, while co-over-expression of both USP44 and USP7 almost completely eliminated FOXP3 polyubiquitination, suggesting a synergistic role of these two DUBs (Fig XREF_FIG C).
USP7 deubiquitinates SPRYD3. 1 / 1
| 1

reach
USP7, which co-IPs with USP11 and can co-IP USP11, RAE1, PAM and SPRYD3 (XREF_SUPPLEMENTARY), efficiently deubiquitinated SPRYD3, whilst RAE1 is only weakly deubiquitinated by USP7 (XREF_FIG).
USP7 deubiquitinates TRIP12. 1 / 1
|

ubibrowser
Ubiquitin-specific protease 7 accelerates p14(ARF) degradation by deubiquitinating thyroid hormone receptor-interacting protein 12 and promotes hepatocellular carcinoma progression
USP7 deubiquitinates KMT2E. 1 / 1
| 1

reach
To determine whether USP7 deubiquitinates MLL5 protein, we used a lentiviral based shRNA approach to eliminate USP7 expression in HeLa cells, and examined the effects on MLL5 protein.
USP7 deubiquitinates PTEN ubiquitinated on K289 on K13. 1 / 1
1 |

biopax:reactome
No evidence text available