USP10 Data Analysis

HGNC Gene Name
ubiquitin specific peptidase 10
HGNC Gene Symbol
USP10
Identifiers
hgnc:12608 NCBIGene:9100 uniprot:Q14694
Orthologs
mgi:894652 rgd:1561965
INDRA Statements
deubiquitinations all statements
Pathway Commons
Search for USP10
Number of Papers
217 retrieved on 2023-02-19

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
ABCD4 ATP binding cassette subfamily D member 4 0.195 0.01 -0.05 9.41e-01
ATP2C2 ATPase secretory pathway Ca2+ transporting 2 0.191 0.04 0.12 7.78e-01
CDK6 cyclin dependent kinase 6 0.181 -0.01 -0.16 8.65e-01
G3BP1 G3BP stress granule assembly factor 1 0.177 BioGRID IntAct INDRA (18) 0.32 1.68 2.72e-09
ZNF146 zinc finger protein 146 0.17 -0.04 -0.30 6.90e-01
GPRIN1 G protein regulated inducer of neurite outgrowth 1 0.167 0.19 0.96 8.99e-04
TGFB3 transforming growth factor beta 3 0.167 0.03 0.10 8.02e-01

Dependency GO Term Enrichment

Gene set enrichment analysis was done on the genes correlated with USP10using the terms from Gene Ontology and gene sets derived from the Gene Ontology Annotations database via MSigDB.

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

GO Identifier GO Name GO Type p-value p-value (adj.) q-value

Transcriptomics

The following table shows the significantly differentially expressed genes after knocking out USP10 using CRISPR-Cas9.

Knockout Differential Expression

Symbol Name log2-fold-change p-value p-value (adj.)
RPL28 ribosomal protein L28 6.22e-01 1.88e-06 4.14e-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 USP10 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 tas hprd trrust ctd vhn pe drugbank omnipath conib crog dgi minerva creeds ubibrowser acsn | geneways tees gnbr semrep isi trips rlimsp medscan eidos sparser reach
USP10 deubiquitinates TP53. 10 / 48
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Because USP10 is a p53 deubiquitinating enzyme, p53 ubiquitination was decreased by transfection of USP10 (compare lanes 3 and 4), whereas deubiquitination of p53 by USP10 was inhibited by co-transfection of USP10 and G3BP1 (compare lanes 4 and 5).

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Furthermore, Beclin1 can alter p53 expression by regulating deubiquitination of p53 by USP10 43.

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Under stress condition, ATM phosphorylates USP10, which then deubiquitinates and targets cytoplasmic p53 back to the nucleus.

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It is likely that USP10 functions to deubiquitinate p53 to counteract the action of E3 ubiquitin ligases such as Mdm2.

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These results demonstrate that USP10 deubiquitinates p53 both in vitro and in vivo.

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Overall, our study demonstrates that resveratrol directly targets G3BP1, which in turn prevents the G3BP1 and USP10 interaction and consequently increases USP10 regulated deubiquitination of p53 (XREF_FIG).

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USP10 is a cytoplasmic ubiquitin-specific protease that deubiquitylates p53, reversing Mdm2-induced p53 nuclear export and degradation [108].

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BECN1 also regulates the stability of the proteins USP10 and USP13, which might explain the novel observation 200 that BECN1 regulates p53 levels, as USP10 mediates p53 deubiquitylation.

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USP10 deubiquitinates both wild-type p53 and mutp53.

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USP10 deubiquitinates p53 and reverses MDM2 mediated nuclear transport and degradation of p53.
USP10 deubiquitinates BECN1. 10 / 10
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Furthermore, the presence of spautin-1 inhibited the deubiquitination of Beclin1 mediated by USP10 and USP13.

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Specific and potent autophagy inhibitor-1 (Spautin-1) was identified to inhibit USP10 and USP13, which deubiquitinate the Beclin 1 subunit of Vsp34 complex, and thus promoted the degradation of Vsp34 PI3 kinase complex.

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It promotes the degradation of Vps34 complexes by inhibiting USP10 and USP13, two ubiquitin specific peptidases that target the deubiquitination of Beclin-1.

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While A20 inhibits PtdIns3P signaling by removing the TRAF6-dependent Lys63-linked chains from Beclin 1, the enzymes USP10 and USP13 prevent PI3K-III complex components from their degradation and, therefore, support autophagy. Interestingly enough, USP10 also stabilizes p53, which, in turn, triggers the degradation of Beclin 1 and VPS34 in order to prevent autophagy.

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Since USP10 mediates the deubiquitination of Beclin1 and reduced levels of USP10 leads to increased ubiquitination and degradation of Vps34 complexes, reduced levels of Vps34 complexes as a result of USP10 reduction may in turn lead to destabilization of USP13.

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We demonstrate that USP10 and USP13 can both mediate the deubiquitination of Beclin1.

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USP10 has also been shown to enhance autophagy by deubiquitinating beclin-1, a component of class-III PI3K complexes that catalyze the formation of phosphatidylinositol 3-phosphate at both autophagy initiation and autophagosome maturation steps.

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USP10 and USP13 have been shown to mediate the deubiquitination of Beclin 1, thereby stabilizing the Vps34 complex XREF_BIBR.

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Inhibition of the Deubiquitinating Enzymes USP10 and USP13 Causes Ubiquitination of Beclin 1.

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Conversely, it was show that Beclin 1 is deubiquitinated by USP10 and USP13 and adding complexity, Beclin 1 itself controlled the protein stabilities of USP10 and USP13 by regulating their deubiquitinating activities, in turn regulating the levels of tumor suppressor p53 [XREF_BIBR].
USP10 deubiquitinates AMPK_alpha. 9 / 9
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Mechanistically, following the energy deprivation, USP10 largely deubiquitinates AMPKalpha so that its activating phosphorylation by LKB1 could be greatly enhanced.

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As shown in XREF_FIG and XREF_SUPPLEMENTARY, knockdown of USP10 increased the ubiquitination of WT AMPKalpha; on the other hand, knockdown of USP10 did not affect ubiquitination levels of the AMPKalpha 4KR mutant (XREF_FIG and XREF_SUPPLEMENTARY).

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We further overexpressed WT USP10 or catalytic inactive mutant in USP10 deficient cells and found that WT USP10, but not the CA mutant decreased ubiquitination of AMPKalpha (XREF_FIG and XREF_SUPPLEMENTARY), suggesting that USP10 regulates AMPKalpha ubiquitination in cells.

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In this study, we identified that USP10 can deubiquitinate PTEN and AMPKalpha and the stabilization of these two proteins will subsequently suppress the activation of AKT and mTOR in HCC cells.

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As shown in Figures 3 E and S3 D, knockdown of USP10 increased the ubiquitination of WT AMPKalpha; on the other hand, knockdown of USP10 did not affect ubiquitination levels of the AMPKalpha 4KR mutan[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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We further overexpressed WT USP10 or CA mutant in USP10 deficient cells and found that WT USP10, but not the CA mutant, decreased ubiquitination of AMPKalpha, suggesting that USP10 regulates AMPKalpha[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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USP10 interacts with AMPK and deubiquitinates AMPKalpha.

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In addition, in line with our study, two different groups have also reported that USP10 deubiquitinates and stabilizes PTEN and AMPKalpha in lung cancer and colon cancer cells [16, 27].

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Recently, it was established that USP10 deubiquitinates AMPKalpha to promote its interaction with LKB1, its master regulator and thus enhances its activity.
USP10 deubiquitinates CFTR. 7 / 7
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Inhibition of USP10 suppresses post-endocytic de-ubiquitination of CFTR, and the cell targets the ion channel to the lysosome rather than recycling it into the apical membrane.

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We previously reported that the DUB USP10 deubiquitinates CFTR in early endosomes of human airway epithelial cells XREF_BIBR.

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In a recent study, we demonstrated that USP10, a host cell DUB, deubiquitinates CFTR in endosomes, thereby reducing the lysosomal degradation of CFTR, and maintaining cell and plasma membrane CFTR XREF_BIBR.

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USP10 decreases the ubiquitination of CFTR, whereas the knockdown of USP10 promotes the ubiquitination and reduction of CFTR at the cell surface [XREF_BIBR].
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Functionally, Cif stabilizes an intracellular complex of a DUB (USP10) and G3BP1, preventing deubiquitylation of CFTR, which is required for recycling the receptor to the plasma membrane XREF_BIBR.

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The ability of USP10 to efficiently deubiquitinate CFTR in the early endosome allows for efficient endocytic recycling of CFTR and thus the long half-life of CFTR (approximately 8-24 h in polarized human airway cells) in the plasma membrane.
USP10 deubiquitinates SIRT6. 7 / 7
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As previously mentioned, the peptidase USP10 de-ubiquitinates SIRT6, thereby protecting it from proteasomal degradation.
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USP10 deubiquitinates and stabilizes the tumor suppressor p53, and SIRT6.

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USP10 suppresses SIRT6 ubiquitination to protect SIRT6 from proteasomal degradation.

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Second, USP10 suppresses SIRT6 ubiquitination and protects SIRT6 from proteasome mediated degradation.

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USP10 deubiquitinates and stabilizes SIRT6, which amplifies the tumor-suppressive activity of SIRT6.

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USP10 negatively regulates SIRT6 ubiquitination.
USP10 deubiquitinates IKBKG. 6 / 6
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MCPIP1 induction serves as a negative feedback mechanism for attenuating NF-kappaB activation in genotoxic response by mediating USP10 dependent deubiquitination of NEMO [13].

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By mediating USP10 dependent deubiquitination of NEMO, MCPIP1 serves in a negative feedback mechanism for attenuation of NF-kappaB activation [XREF_BIBR].

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One example is USP10 that requires the protein MCPIP-1 (monocyte chemotactic protein induced protein 1) to interact with and deubiquitinate its substrate NEMO inhibiting the NF-kappaB signalling cascade [XREF_BIBR].

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USP10 deubiquitinates IKKgamma and NEMO, thereby inhibiting IKKgamma mediated nuclear factor kappaB (NF-kappaB) activation after genotoxic stress.

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Thus, by mediating USP10 dependent deubiquitination of NEMO, MCPIP1 induction serves as a negative feedback mechanism for attenuating genotoxic NF-kappaB activation.
USP10 deubiquitinates PCNA. 5 / 5
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Moreover, USP10 could induce PCNA deubiquitination to promote HCC cell growth.

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And USP10 could strengthen cell proliferative and migratory abilities through deubiquitinating PCNA.

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Recent research has shown that PCNA is also modified by ISG15, and ISGylation of PCNA recruits USP10 to deubiquitinate PCNA, thereby regulating PCNA ubiquitination under UV irradiation induced stress.

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An interesting study has recently shown that the deubiquitylation of mammalian PCNA, at least in the context of DNA damage induced by ultraviolet irradiation (UV), is aided by the deubiquitylating activity of USP10.

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This modification in turn recruits USP10 that de-ubiquitylates PCNA in order to block TLS and resume normal replication.
USP10 deubiquitinates NLRP7. 4 / 4
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NLRP7 deubiquitination by USP10 promotes tumor progression and tumor associated macrophage polarization in colorectal cancer.

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Collectively, the present results indicated that NLRP7 in CRC cells interacts with and is deubiquitinated by USP10, resulting in increased NLRP7 protein stability.

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Co-IP experiments showed that USP10 knockdown increased the ubiquitination of NLRP7 in HCT116 cells.

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NLRP7 deubiquitination by USP10 promotes tumor progression and tumor-associated macrophage polarization in colorectal cancer.
USP10 deubiquitinates PTEN. 4 / 4
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We further demonstrated that USP10 directly interacted with and stabilized PTEN via deubiquitination.

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Additionally, we found that USP10 stabilized PTEN protein in a dose dependent manner, and inhibited Lys-48-linked polyubiquitylation of PTEN.

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In addition, in line with our study, two different groups have also reported that USP10 deubiquitinates and stabilizes PTEN and AMPKalpha in lung cancer and colon cancer cells [16, 27].

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In this study, we identified that USP10 can deubiquitinate PTEN and AMPKalpha and the stabilization of these two proteins will subsequently suppress the activation of AKT and mTOR in HCC cells.
USP10 deubiquitinates Histone. 3 / 3
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USP10 deubiquitylates the histone variant H2A.Z and both are required for androgen receptor mediated gene activation.

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Moreover, USP10 not only binds AR, resulting in increased transcriptional activity, but also deubiquitinates the histone variant H2A.Z, both of which are required for AR - mediated gene activation [XREF_BIBR, XREF_BIBR].

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In addition, more bulky structures, SUMO (small ubiquitin related modifier) and ubiquitin are conjugated to histones (Galanty et al., 2009; Morris et al., 2009; Shioo and Eisenman, 2003; Thakar et al.[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
USP10 deubiquitinates His2Av. 3 / 3
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USP10 specifically deubiquitylates H2A.Z and H2A.

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USP10 directly deubiquitylates H2A.Z in vitro and in vivo, and reducing USP10 expression in prostate cancer cells results in elevated steady-state levels of mono-ubiquitylated H2A.Z (H2A.Zub1).

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In addition, the deubiquitination of H2A.Z by USP10 is required for the androgen-receptor mediated transcriptional activation of hormone regulated genes [XREF_BIBR].
USP10 deubiquitinates TBP. 3 / 3
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To test whether USP10 deubiquitinates and stabilizes TBP in mammalian cells, we overexpressed USP10 in 293T cells and monitored TBP ubiquitination levels in these cells.

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To test whether USP10 deubiquitinates TBP through direct protein protein interactions, we used HA-TBP to co-IP with Flag-USP10 co-expressed in 293T cells.

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Huwe1 as an E3 ligase targeting TBP for K48-linked ubiquitination and proteasome-mediated degradation; We found that Huwe1 activity on TBP is antagonized by the deubiquitinase USP10, which protects TBP from degradation.
USP10 deubiquitinates TRAF6. 3 / 3
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We found TANK formed a complex with MCPIP1 (also known as ZC3H12A) and a deubiquitinase, USP10, which was essential for the USP10-dependent deubiquitination of TRAF6 and the resolution of genotoxic NF-κB activation upon DNA damage.

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TRAF Family Member associated NF-kappaB Activator (TANK) Inhibits Genotoxic Nuclear Factor kappaB Activation by Facilitating Deubiquitinase USP10 dependent Deubiquitination of TRAF6 Ligase.

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We found TANK formed a complex with MCPIP1 (also known as ZC3H12A) and a deubiquitinase, USP10, which was essential for the USP10 dependent deubiquitination of TRAF6 and the resolution of genotoxic NF-kappaB activation upon DNA damage.
USP10 deubiquitinates SKP2. 2 / 2
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Additionally, Liao and colleagues [XREF_BIBR] found that USP10 can promote leukemic cell proliferation by deubiquitinating and stabilizing the S-phase kinase associated protein 2 (SKP2) that acts as a co-regulator of BCR-ABL mediating its K63 linked ubiquitination and activation in CML cells [XREF_BIBR].

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USP10 deubiquitinates and stabilizes SKP2.
USP10 deubiquitinates RPS3. 2 / 2
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Subsequent deubiquitination of RPS2 and RPS3 by USP10 is critical for recycling of stalled ribosomes in a process known as ribosome associated quality control.

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No evidence text available
USP10 deubiquitinates HDAC6. 2 / 2
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XREF_FIG, wild-type USP10, but not the catalytically-inactive USP10CA mutant, significantly reduces HDAC6 ubiquitination in 293T cells (comparing lanes 3 and 4 in the top panel).

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Next, we tested whether USP10 could deubiquitinate HDAC6.
USP10 deubiquitinates MSH2. 2 / 2
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USP10 deubiquitinates MSH2 in vitro and in vivo Moreover, the protein level of MSH2 is positively correlated with the USP10 protein level in a panel of lung cancer cell lines.

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Here we report that ubiquitin-specific peptidase 10 (USP10) interacts with and stabilizes MSH2.
USP10 leads to the deubiquitination of CDKN2A. 2 / 2
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USP10, in turn, mediated the deubiquitination of p14ARF, preventing its proteasome dependent degradation.

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Oncogene-induced senescence mediated by c-Myc requires USP10 dependent deubiquitination and stabilization of p14ARF.
USP10 leads to the deubiquitination of mutated TP53. 2 / 2
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However, it is unclear whether USP10 antagonizes ubiquitination of mutp53 by other ubiquitin ligases, USP10 alters subcellular localization of mutp53, and USP10 plays a role in deubiquitination of different TP53 mutants.

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USP10 deubiquitinates and stabilizes both wt and mutant p53.
USP10 deubiquitinates TOP2A. 1 / 1
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In contrast, USP10, also a cytosolic DUB [XREF_BIBR], deubiquitylates TOP2A in complex with the E3 ligase RNF168 [XREF_BIBR], which is also important in DNA damage response signalling for double-strand break repair [XREF_BIBR].
USP10 deubiquitinates AMPK. 1 / 1
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Deubiquitination and activation of AMPK by USP10.
USP10 deubiquitinates PRKAA2. 1 / 1
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The deubiquitinase USP10 specifically removes ubiquitination on AMPKalpha to facilitate AMPKalpha phosphorylation by LKB1.
USP10 deubiquitinates PDLIM5. 1 / 1
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Research on the endothelium revealed that USP10, as a regulatory protein, delayed the rate of NICD1 degradation by deubiquitinating the Notch1 receptor (Lim et al., 2019).
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Unubiquitinated USP10 leads to the deubiquitination of CFTR. 1 / 1
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In P. aeruginosa, the OMV associated toxin CFTR-inhibitory factor (Cif) controls the host deubiquitylating enzyme USP10 to cause increased ubiquitylation of cystic fibrosis transmembrane conductance regulator (CFTR), which is involved in mucus production.
USP10 deubiquitinates H2AZ1. 1 / 1
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USP10 leads to the deubiquitination of SLC9A3. 1 / 1
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Ubiquitin specific peptidase 7 (USP7) and USP10 mediate deubiquitination of human NHE3 regulating its expression and activity.
USP10 deubiquitinates MDM4. 1 / 1
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Another DUB, USP10 deubiquitinates p53, but not MDM2 or MDMX.
USP10 deubiquitinates AR. 1 / 1
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Together, these data provide novel insights into how H2A.Z ubiquitylation and deubiquitylation and USP10 function in AR regulated gene expression.
Modified USP10 leads to the deubiquitination of AMPK_alpha. 1 / 1
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In contrast, overexpression of USP10 significantly inhibited polyubiquitylation of PTEN and AMPKalpha.
USP10 deubiquitinates ITGB1. 1 / 1
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?Silencing of the DUB USP10 induces a buildup of ubiquitin on integrins beta1 and beta5 in cell lysates, whereas recombinant USP10 removes ubiquitin from these integrin subunits.
USP10-C424A deubiquitinates TP53. 1 / 1
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We confirmed that wild-type USP10 but not USP10 C424A deubiquitinates the p53 protein (XREF_SUPPLEMENTARY C).
Modified USP10 leads to the deubiquitination of PTEN. 1 / 1
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In contrast, overexpression of USP10 significantly inhibited polyubiquitylation of PTEN and AMPKalpha.
USP10 deubiquitinates ULK1. 1 / 1
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However, a direct deubiquitination of ULK1 by USP10 remains to be demonstrated.
Mutated USP10 leads to the deubiquitination of BECN1. 1 / 1
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As shown in XREF_FIG, the coincubation of ubiquitinated Beclin1 with USP10 or USP13 but not a catalytically inactive USP10 mutant reduced the levels of Beclin1 ubiquitination.
USP10 deubiquitinates NOTCH1. 1 / 1
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Research on the endothelium revealed that USP10, as a regulatory protein, delayed the rate of NICD1 degradation by deubiquitinating the Notch1 receptor (Lim et al., 2019).
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USP10 deubiquitinates AICDA. 1 / 1
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USP10 regulates B cell response to SARS-CoV-2 or HIV-1 nanoparticle vaccines through deubiquitinating AID.
USP10 deubiquitinates TBX21. 1 / 1
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USP10 deubiquitinates ITGB5. 1 / 1
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?Silencing of the DUB USP10 induces a buildup of ubiquitin on integrins beta1 and beta5 in cell lysates, whereas recombinant USP10 removes ubiquitin from these integrin subunits.
USP10 deubiquitinates ENaC. 1 / 1
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Yet, overexpressed USP10 does not deubiquitinate the bulk of the ENaC pool.
USP10 deubiquitinates H2BC10. 1 / 1
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The deubiquitinase (DUB) Ubp10 is thought to promote heterochromatic silencing by maintaining low H2B-Ub at sub-telomeres
USP10 deubiquitinates PRKAA1. 1 / 1
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The deubiquitinase USP10 specifically removes ubiquitination on AMPKa to facilitate AMPKa phosphorylation by LKB1.
USP10 deubiquitinates FLT3. 1 / 1
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USP10, a primary cytoplasmic DUB, acts as an oncogene or a tumor suppressor by regulating various protein substrates, including FLT3, p53, AMPK, PTEN, etc.
USP10 leads to the deubiquitination of mutated FLT3. 1 / 1
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Given our recent finding that USP10 deubiquitinates mutant FLT3, 18 coupled with reported studies showing that FLT3 and SYK are interacting partners with each other and are targets of the same E3 ligase c-CBL, XREF_BIBR, XREF_BIBR, XREF_BIBR - XREF_BIBR we hypothesised that USP10 may play a role in stabilisation of SYK.
USP10 deubiquitinates SNX3. 1 / 1
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?A two-hybrid screen identified sorting nexin 3 (SNX3) as a novel substrate of Usp10.
Modified USP10 leads to the deubiquitination of TBP. 1 / 1
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Strikingly, overexpression of USP10 significantly inhibited TBP ubiquitination (XREF_FIG).
Modified USP10 leads to the deubiquitination of mutated TP53. 1 / 1
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Coexpression of USP10 together with Mdm2 decreased mutant p53 ubiquitination (XREF_SUPPLEMENTARY), while downregulation of USP10 increased mutant p53 ubiquitination (XREF_SUPPLEMENTARY), suggesting that USP10 also regulates mutant p53 ubiquitination.
USP10 deubiquitinates RPS2. 1 / 1
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Subsequent deubiquitination of RPS2 and RPS3 by USP10 is critical for recycling of stalled ribosomes in a process known as ribosome associated quality control.
USP10 deubiquitinates SNAI2. 1 / 1
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Here, by using a genome wide siRNA screen for human deubiquitinating enzymes (DUBs), we identified USP10 as a deubiquitinase for Slug in cancer cells.
Modified USP10 leads to the deubiquitination of SIRT6. 1 / 1
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The results showed that overexpression of wild-type USP10 promoted the deubiquitination of Sirt6 and inhibited the activation of downstream Akt signaling pathway, while mutant USP10 lost this function.
USP10 deubiquitinates Nucleoproteins. 1 / 1
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The result showed that both USP10 and USP11 specifically co-precipitated with NP-HA (lanes 1, 3 and 4, lower panel), consistent with the published result, and NP could be deubiquitinated by only USP11 but not USP10 (lanes 3 and 4, upper panel).
USP10 deubiquitinates TAP1. 1 / 1
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USP10 deubiquitinates MDM2. 1 / 1
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Another DUB, USP10 deubiquitinates p53, but not MDM2 or MDMX.

Other Statements

psp cbn pc bel_lc signor biogrid tas hprd trrust ctd vhn pe drugbank omnipath conib crog dgi minerva creeds ubibrowser acsn | geneways tees gnbr semrep isi trips rlimsp medscan eidos sparser reach
USP10 affects TP53
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USP10 activates TP53.
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USP10 activates TP53. 10 / 24
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We identify 9 direct binding partners of p53 in the nuclear RNA interactome, including USP10, which deubiquitinates and activates p53 in response to DNA damage, and Sumo1, which can itself become covalently coupled to p53 to regulate its activity and subcellular localization (XREF_SUPPLEMENTARY) XREF_BIBR XREF_BIBR XREF_BIBR.

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Upon DNA damage, USP10 deubiquitylates and activates p53.

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USP10 , upon ATM-dependent phosphorylation at threonine 42 and serine 337 residues , is stabilized and translocated to the nucleus to activate p53 through deubiquitinating activity , inducing tumor cell suppression [ 53 ] .
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Overall, these results suggest that USP10 potentiates p53 function in cells.

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Thus , depletion of USP10 would cause a decrease in p53 levels and lead to cisplatin resistance .

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For example, USP7 regulates the stability of both p53 and Mdm2 and maintains p53 ubiquitination levels; 120 USP2 mediates the stability of Mdm2; 121 USP10 modulates p53 localization and stability; 122 OTUB1 abrogates p53 ubiquitination and activates p53.

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USP10 modulates anterograde and retrograde vesicular trafficking, the localization and stability of p53 and binds Dengue virus RNA.

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Wildtype TP53 is usually rescued from proteasomal degradation by USP10.

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As shown in XREF_FIG, downregulation of USP10 increased cancer cell proliferation in p53 +/+ cells, while USP10 expression levels have no apparent effect on proliferation in cells lacking p53.

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It will be interesting to discover whether overexpression of USP7 could also rescue the diminished DNA damage induced p53 response caused by USP10 depletion.
USP10 activates mutated TP53. 2 / 2
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Paradoxically, USP10 could promote cancer cell proliferation in mutant p53 background.

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Furthermore, expression of USP10 increased mutant p53 stability (XREF_SUPPLEMENTARY), while downregulation of USP10 decreased mutant p53 stability (XREF_SUPPLEMENTARY), suggesting that USP10 regulates mutant p53 stability.
USP10 inhibits TP53.
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USP10 inhibits TP53. 10 / 20
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Expression of USP10 significantly suppressed c-Myc transcriptional activity in p53 wildtype and p53 -/- HCT116 cells, but the levels of USP10 mediated suppression in c-Myc target gene transcription in p53-null cells were partially reversed.

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In addition, USP10 suppresses the tumour cell growth in cells with wild-type p53, and USP10 expression is down-regulated in a high percentage of clear cell carcinomas known to have few p53 mutations [108].

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It also binds USP10, a key p53 regulator, reducing p53 stability and its anti-cancer functions.

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Indeed, USP10 depletion attenuates DNA damage induced stabilization of p53, an effect that was rescued by overexpression of wild-type USP10 but not by mutant USP10 lacking ATM phosphorylation sites.

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Consistent with this notion, USP10 expression is frequently lost in renal cell carcinoma, and overexpression of USP10 suppresses cell transformation and tumorigenesis in a p53 dependent fashion.

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Coexpression of WT USP10 with Mdm2 reversed Mdm2 induced cytoplasmic translocation of p53.

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Association of USP10 with G3BP2 Inhibits p53 Signaling and Contributes to Poor Outcome in Prostate Cancer.

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It also binds USP10, a key p53 regulator, reducing p53 stability and anti-cancer functions.

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Downregulation of p53 abolished the inhibitory effect of USP10 on tumor growth (XREF_FIG and data not shown), confirming that USP10 inhibits cancer cell growth by stabilizing p53.

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Usp10 overexpression abolished the estrogen mediated regulation of p53 and the downstream transcriptional gene p21.
USP10 inhibits mutated TP53. 1 / 1
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Furthermore, expression of USP10 increased mutant p53 stability (XREF_SUPPLEMENTARY), while downregulation of USP10 decreased mutant p53 stability (XREF_SUPPLEMENTARY), suggesting that USP10 regulates mutant p53 stability.
USP10 bound to G3BP2 inhibits TP53. 1 / 1
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For example, USP10 interacts with G3BP2 to block p53 signal transduction, leading to poor prognosis in prostate cancer [XREF_BIBR]; USP44 promotes the development of prostate cancer by stabilizing EZH2 [XREF_BIBR], and USP2a enhances c-Myc expression via microRNA related regulation and thus promotes tumourigenesis [XREF_BIBR].
USP10 increases the amount of TP53.
| 9
USP10 increases the amount of TP53. 5 / 6
| 5

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Reconstitution of USP10 in CAKI-1 and CAKI-2 (WT p53 cell lines) restored p53 expression and increased p21 and BAX expression (XREF_SUPPLEMENTARY).

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In accordance with published work, we detected that knockdown of USP10 is sufficient to reduce p53 protein levels.

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Both, the DUB HAUSP (herpesvirus associated ubiquitin specific protease) and USP10 (ubiquitin specific protease 10), targeting poly-ubiquitinated p53, have been shown to restore p53 levels even when Hdm2 is overexpressed.

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These results suggest that USP10 can upregulate p53 levels, most likely by deubiquitinating and consequently stabilizing p53.

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In accordance with published work, we detected that knockdown of USP10 is sufficient to reduce p53 protein levels (Yuan et al., 2010).
Modified USP10 increases the amount of TP53. 3 / 3
| 3

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Furthermore, overexpression of USP10 in 786-O cells increases levels of mutp53, leading to enhanced colony formation and proliferation, which is nullified by depletion of mutp53.

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Overexpression of USP10 significantly increased the levels of endogenous p53, with no effect on p53 mRNA levels (XREF_FIG).

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Consistent with this study, we show that increased USP10 expression in mutant p53 background increases p53 levels and promotes cancer cell proliferation, while downregulation of USP10 inhibits cancer cell growth.
USP10 increases the amount of mutated TP53. 1 / 1
| 1

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Inhibition of USP10 by the protein spautin-1 reduces mutant p53 levels under glucose restricted conditions.
USP10 decreases the amount of TP53.
| 4
USP10 decreases the amount of TP53. 4 / 4
| 4

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Interestingly, downregulation of USP10 significantly decreased p53 stabilization and the expression of p53 target genes p21 and Bax after DNA damage (XREF_FIG).

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On the other side, the ubiquitinated TP53 could be reversed and stabilized by USP7 and USP10, to keep the amount of TP53 in check.

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Thus, depletion of USP10 would cause a decrease in p53 levels and lead to cisplatin resistance.

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To confirm the role of USP10 in regulating p53 levels, we depleted USP10 using USP10 specific shRNA, and found that downregulation of USP10 decreased p53 protein levels with no effect on p53 mRNA levels (XREF_FIG).
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USP10 Is an Essential Deubiquitinase for Hematopoiesis and Inhibits Apoptosis of Long-Term Hematopoietic Stem Cells.

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Collectively, these results indicate that USP10 inhibits cytokine deprivation induced apoptosis of IVC-LSK cells in a deubiquitinase dependent but ROS independent manner.

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XREF_FIG, overexpression of either HDAC6 or USP10 in USP10 knockdown cells significantly increased cell survival post-cisplatin treatment and reduced apoptosis as shown by the level of cleaved PARP-1.

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Thus, USP10 induced aggregates and aggresomes might inhibit apoptosis by reducing the amount of ubiquitinated protein oligomers.

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USP10 also has deubiquitinase independent functions, such that USP10 inhibits apoptosis by reducing reactive oxygen species (ROS) production induced by an oxidative stress inducer arsenite.

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A deubiquitinase-inactive USP10 mutant (USP10/C418A) did not inhibit cytokine deprivation-induced apoptosis of IVC-LSK cells, indicating that a factor deubiquitinated by USP10 inhibits apoptosis of IVC-LSK cells.

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We previously reported that USP10 inhibits oxidant-induced apoptosis by reducing ROS production in mouse embryonic fibroblasts (MEFs) ( xref ).

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However, we could not exclude the possibility that USP10 inhibits apoptosis by promoting degradation of pro-apoptotic protein(s) by aggresome-mediated autophagy.

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Upon exposure to an oxidant, USP10 inhibits ROS-dependent apoptosis by reducing ROS production ( xref ).

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On exposure to arsenic, an oxidative stress inducer, USP10 is recruited into stress granules (SGs), and USP10 containing SGs reduce reactive oxygen species (ROS) production and inhibit ROS dependent apoptosis.
USP10 bound to G3BP1 inhibits apoptotic process. 1 / 1
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Studies using USP10 mutants, including USP10/77 -792 and USP10/95-792, indicate that USP10 's interaction with G3BP1 is essential for inhibition of ROS dependent apoptosis and for USP10 incorporation into stress granules.
| 4

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In conclusion, these results suggest that USP10 promotes proliferation and migration and inhibits apoptosis of endometrial stromal cells in endometriosis through activating the Raf-1/MEK/ERK pathway.

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USP10-knockout indicated that USP10, through augmenting formation of SGs, reduced reactive oxygen species (ROS) production and inhibited ROS dependent apoptosis.
| PMC

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USP10 promotes proliferation and migration and inhibits apoptosis of endometrial stromal cells in endometriosis through activating the Raf-1/MEK/ERK pathway.

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USP10 Heterozygote mice exhibited exacerbated hepatic I/R injury, as evidenced by enhanced liver inflammation via the NF-kappaB signalling pathway and increased hepatocyte apoptosis.

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Two independent USP10 short hairpin RNAs (shRNAs) both promoted cell proliferation of HCCLM3 and HUH7 cells.

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In vitro data showed that USP10 deficiency reduced proliferation and migration of rat thoracic aorta smooth muscle cells (A7r5) and human aortic smooth muscle cells (HASMCs).

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Indeed, downregulation of USP10 decreases p53 stability and increases cancer cell proliferation XREF_BIBR, thus projecting a role as a tumor suppressor.

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Proliferation inhibition by loss of USP10 depends on SKP2 functional status.

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In conclusion, these results suggest that USP10 promotes proliferation and migration and inhibits apoptosis of endometrial stromal cells in endometriosis through activating the Raf-1/MEK/ERK pathway.

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USP10 promotes proliferation and migration and inhibits apoptosis of endometrial stromal cells in endometriosis through activating the Raf-1/MEK/ERK pathway.

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For example, in hepatocellular carcinoma, Zhu et al. reported that USP10 promotes proliferation [XREF_BIBR], whereas Lu et al. found that USP10 suppresses tumor progression by inhibiting mTOR activation [XREF_BIBR].

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Specifically, USP10 activates PTEN by preventing its K63 linked polyubiquitination mediated by TRIM25 and suppresses the AKT and mTOR signaling pathway thereby inhibiting NSCLC proliferation, indicating that it may be a potential drug target for cancer treatment.

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USP10 overexpression promoted ectopic endometrial stromal cell migration and proliferation, suppressed cell apoptosis, and activated MEK and ERK signaling that is a critical downstream target of the serine/threonine protein kinase Raf-1, which was significantly blocked by PD98059.

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USP10 regulates Musashi-2 stability via deubiquitination and promotes tumour proliferation in colon cancer.

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Consistent with this study, we show that increased USP10 expression in mutant p53 background increases p53 levels and promotes cancer cell proliferation, while downregulation of USP10 inhibits cancer cell growth.

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Conversely, downregulation of USP10 inhibited cell proliferation (XREF_FIG and data not shown).

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As expected, USP10 over expression inhibited the proliferation of colon cancer cells with either a wildtype p53 or with p53-deficency.

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The deubiquitinase USP10 restores PTEN activity and inhibits non small cell lung cancer cell proliferation.

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Furthermore, the double knock-down of G3BP1 and USP10 rescued the inhibition of proliferation induced by G3BP1 depletion in HCT116 (XREF_FIG) and SK-MEL-5 cells (XREF_SUPPLEMENTARY).

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Furthermore, we provide evidence that USP10 inhibits cancer cell proliferation in cells with WT p53.

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Consistent with its molecular activity, re-expression of USP10 suppressed NSCLC cell proliferation and migration while knockout of USP10 promoted NSCLC cell proliferation and migration.

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On the other hand, reconstitution of USP10 in cells with USP10 downregulation inhibited cancer cell proliferation (XREF_FIG), suggesting the effect of USP10 knockdown is specific.

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In contrast, overexpressing USP10 expression in MHCC97L and BEL-7402 cells reduced the cell proliferation.

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Furthermore, we provide evidence that USP10 inhibits cancer cell proliferation in cells with WT p53.

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Conversely, downregulation of USP10 inhibited cell proliferation ( xref and data not shown).
USP10 affects MYC
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USP10 inhibits MYC.
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USP10 inhibits MYC. 10 / 22
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Third, USP10 antagonizes c-Myc transcriptional activity and cell cycle progression through both SIRT6 and p53.

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Previous studies have shown that USP10 antagonizes c-Myc transcriptional activation that could promote Sirt6 stabilization to suppress tumor formation.

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It has been reported that one of the molecular mechanisms underlying USP10 tumor-suppressive functions is that it protects p53 from degradation, raising the possibility that USP10 also antagonizes c-Myc transcriptional activity through p53.

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In addition, p53 knockdown partially abolished USP10 over-expression-mediated suppression in c-Myc target gene expression in SIRT6 +/+ MEFs, and p53 knockdown in SIRT6 -/- MEFs fully reversed USP10 mediated suppression of c-Myc targets expression (XREF_FIG).

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To further prove the principle that USP10 suppresses c-Myc transcriptional activity through both SIRT6 and p53, we tested whether knockdown of SIRT6 rescues this USP10 suppressive activity.

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USP10 suppresses c-Myc transcriptional activity through SIRT6 and p53.

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We then used SIRT6-null mouse embryonic fibroblasts (MEFs) to prove the principle that SIRT6 is another downstream factor in USP10 mediated c-Myc suppression.

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USP10 inhibits c-Myc transcriptional activity.

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Therefore, USP10 might antagonize c-Myc activity to inhibit tumor cell growth though SIRT6 and p53.

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We then used in vitro anchorage independent colony formation assay and analyzed the role of USP10 mediated c-Myc suppression in tumor formation.
USP10 activates MYC.
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USP10 activates MYC. 2 / 2
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Thus, we determined whether USP10 functions as a tumor suppressor through SIRT6 mediated c-Myc inactivation.

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To our surprise, SIRT6 gene suppression resulted in a lower level of increase in c-Myc target gene expression than that of USP10 knockdown, implying that additional factors may contribute to USP10 mediated c-Myc suppression.
USP10 decreases the amount of MYC.
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USP10 decreases the amount of MYC. 1 / 1
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USP10 also antagonizes c-myc transcription through deubiquitination of SIRT6, a histone deacetylase, and NF-kappaB signaling through deubiquitination of NEMO [XREF_BIBR].
USP10 affects SIRT6
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USP10 inhibits SIRT6.
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USP10 inhibits SIRT6. 1 / 13
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Accordingly, inactivation of USP10 reduced Sirt6 abundance and stability and diminished Sirt6 induced downstream signaling in cardiomyocytes.
USP10 activates SIRT6.
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USP10 activates SIRT6. 5 / 8
| 1 4

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Furthermore, USP10 directly regulates Sirt6 during the pathogenesis of CH.

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These studies suggest the possibility that the association with RBM5-AS1 may reinforce USP10 dependent suppression of SIRT6 degradation.
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In contrast, knockdown of USP10 but not USP22 in RKO cells promoted SIRT6 degradation.

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It was shown that knockdown of USP10 decreased Sirt6 expression , whereas overexpression of USP10 increased Sirt6 protein expression in primary cardiomyocytes after Ang II stimulation ( Figure 6C and 6D ) .

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Therefore, it seems that USP10 mediated SIRT6 stabilization is largely involved in regulating c-Myc transcriptional activity.
USP10 increases the amount of SIRT6.
| 3
USP10 increases the amount of SIRT6. 2 / 2
| 2

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It was shown that knockdown of USP10 decreased Sirt6 expression, whereas overexpression of USP10 increased Sirt6 protein expression in primary cardiomyocytes after Ang II stimulation.

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Conversely, shRNA mediated knockdown of USP10 decreased the endogenous SIRT6 protein levels without affecting SIRT6 mRNA levels (XREF_FIG).
Modified USP10 increases the amount of SIRT6. 1 / 1
| 1

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It was shown that knockdown of USP10 decreased Sirt6 expression, whereas overexpression of USP10 increased Sirt6 protein expression in primary cardiomyocytes after Ang II stimulation.
USP10 affects cell growth
| 19
USP10 inhibits cell growth.
| 18
| 17

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In addition, USP10 suppresses the tumour cell growth in cells with wild-type p53, and USP10 expression is down-regulated in a high percentage of clear cell carcinomas known to have few p53 mutations [108].

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Downregulation of p53 abolished the inhibitory effect of USP10 on tumor growth (XREF_FIG and data not shown), confirming that USP10 inhibits cancer cell growth by stabilizing p53.

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In addition, USP10 suppresses the tumour cell growth in cells with wild-type p53, and USP10 expression is down-regulated in a high percentage of clear cell carcinomas known to have few p53 mutations [XREF_BIBR].

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Given USP10 also regulates p53 expression and suppresses tumor cell growth, phosphorylation of USP10 under energy stress might contribute to p53 level increase and tumor suppression.

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On the other hand, shRNA mediated USP10 knockdown caused more vigorous tumor cell growth of both wildtype and p53-null cells, confirming the tumor-suppressive function of USP10 (XREF_FIG, XREF_SUPPLEMENTARY).

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Moreover, USP10 inhibited cell growth and invasion in lung cancer [XREF_BIBR], and was an independent factor for the prognosis of gastric carcinoma [XREF_BIBR].
| PMC

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Consistent with this study, we show that increased USP10 expression in mutant p53 background increases p53 levels and promotes cancer cell proliferation, while downregulation of USP10 inhibits cancer cell growth.

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3.2 Spautin-1, a dual USP10 and USP13 antagonist, inhibits melanoma cell growth in vitro.
| PMC

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Our study demonstrated that USP10 suppresses tumor cell growth through potentiating both SIRT6- and p53 mediated suppression of the oncogene c-myc.

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The same study shows that USP10 suppresses tumor cell growth in cells expressing wild-type p53.
Modified USP10 inhibits cell growth. 1 / 1
| 1

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Consistent with this study, we show that increased USP10 expression in mutant p53 background increases p53 levels and promotes cancer cell proliferation, while downregulation of USP10 inhibits cancer cell growth.
USP10 activates cell growth.
| 1
| 1

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On the other hand, in cancer cells with mutant p53, USP10 could promote cancer cell growth, and inhibition of USP10 is called for.
USP10 affects cell death
| 5 16
USP10 inhibits cell death.
| 5 12
| 5 10

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To obtain information describing how USP10 inhibits MG-132-induced cell death, we measured cell death of USP10-KD cells expressing several USP10 mutants.

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USP10 inhibited cell death induced by PI, and the inhibition correlated with aggresome/aggregate-inducing activity ( xref and xref ).

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Given that USP10-WT, USP10 C424A, and USP10 96-798, but not USP10 1-214, in USP10-KD cells promoted p62 aggregation and aggresome formation (XREF_FIG G and XREF_SUPPLEMENTARY A-S5C), these results suggested that USP10 inhibits cell death induced by MG-132 by promoting aggresome formation and p62 aggregation.

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Thus, we examined whether USP10 inhibits MG-132-induced cell death by measuring activated caspase-3 (cleaved caspase-3).

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Thus, we examined whether USP10 inhibits MG-132-induced cell death by measuring activated caspase-3 (cleaved caspase-3).

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USP10 Inhibits Cell Death Induced by MG-132.

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USP10 C424A and USP10 96-798, but not USP10 1-214, reduced cell death of USP10-KD cells (XREF_FIG G and XREF_SUPPLEMENTARY A-S5C).

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USP10 inhibited cell death induced by PI, and the inhibition correlated with aggresome and aggregate inducing activity (XREF_FIG and XREF_SUPPLEMENTARY).

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Similar to Beclin 1 knockdown, we found that suppression of the ubiquitin specific peptidase, USP10, or a small molecule inhibitor of the deubiquitinases USP10 and USP13, i.e., spautin-1 XREF_BIBR, can increase radiation induced DSBs and promote tumor cell death.

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These results indicated that USP10 and p62 cooperatively inhibit MG-132-induced cell death by promoting the formation of aggresomes and p62 aggregates.
USP10-C424A inhibits cell death. 1 / 1
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USP10 C424A and USP10 96-798, but not USP10 1-214, reduced cell death of USP10-KD cells (XREF_FIG G and XREF_SUPPLEMENTARY A-S5C).
Mutated USP10 inhibits cell death. 1 / 1
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While USP10/77 -792 and USP10/95 -792 mutants inhibited cell death of IVC-LSK cells as efficiently as USP10-WT, a deubiquitinase inactive mutant USP10 and C418A showed minimal activity and failed to inhibit cytokine deprivation induced cell death after 44and 62hr of starvation.
USP10 activates cell death.
| 4
| 4

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Similar to Beclin 1 knockdown, we found that suppression of the ubiquitin specific peptidase, USP10, or a small molecule inhibitor of the deubiquitinases USP10 and USP13, i.e., spautin-1 XREF_BIBR, can increase radiation induced DSBs and promote tumor cell death.

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Consistent with our screening results on the effect of USP10 siRNA, pretreatment with spautin-1, a specific inhibitor of USP10, markedly inhibited curcumin induced morphological changes of mitochondria and subsequent paraptotic cell death in various breast cancer cells.

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Additional work will be needed to investigate the detailed underlying mechanism by which USP10 contributes to paraptotic cell death in malignant breast cancer cells.

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Additional work is needed to investigate the detailed underlying mechanism by which USP10 contributes to mitochondrial dilation and subsequent paraptotic cell death in malignant breast cancer cells.
G3BP1 affects USP10
| 3 13
G3BP1 inhibits USP10.
| 3 12
| 3 9

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discovered the interaction of G3BP1 with ubiquitin specific protease 10 (USP10), and they concluded that G3BP1 might restrict the deubiquitinating activity of USP10.

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It should be remarked that G3BP1 is also a perturbator for the PD-VPs USP10 [91], GiGYF2 [99], EIF4G1 [100], and TIAL1 [101].

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G3BP1 disrupts the interaction of USP10 with p53.

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Anisonov et al. [91] also found that USP10 is inhibited by G3BP1 in a mechanism similar to that for NUP62, which indicates an analogous cascading route from SARS-CoV-2 to PD for this protein.

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One of the reported functions of G3BP1 is to bind to and inhibit USP10 XREF_BIBR.

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Surprisingly, the human homolog of Bre5, G3BP1, inhibits the activity of USP10, at least in vitro, indicating that cofactors can either restrict or enhance protease activity.

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Notably, siRNA mediated knockdown of G3BP1 significantly increased the abundance of CFTR, most likely because endogenous G3BP1 inhibits USP10 (XREF_FIG).

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It appears therefore that the FGDF mediated G3BP and USP10 complex is mutually inhibitory, with G3BP inhibiting the DUB activity of USP10 and USP10 inhibiting the SG nucleating function of G3BP.

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Anisonov et al. [91] also found that USP10 is inhibited by G3BP1 in a mechanism similar to that for NUP62, which indicates an analogous cascading route from SARS-CoV-2 to PD for this protein.

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In airway epithelial cells treated with the CFTR inhibitory factor (Cif), the Ras GTPase-activating protein-binding protein 1 (G3BP1) inhibits the ubiquitin-specific protease USP10.
G3BP1 bound to USP10 inhibits USP10. 3 / 3
| 3

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G3BP1 binds to USP10 and therefore disrupts the interaction of USP10 with p53, leading to suppression of p53 deubiquitination.

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Second, in U2OS bladder cancer cells, the interaction between G3BP1 and USP10 inactivates the deubiquitinating enzyme activity of USP10 XREF_BIBR.

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G3BP1 binds to USP10 and inhibits the deubiquitination activity of USP10.
G3BP1 activates USP10.
| 1
G3BP1 activates USP10. 1 / 1
| 1

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Interestingly G3BP1 modulates USP10 deubiquitinase activity, as well as interacts and co-localizes with HCV NS5B protein and RNA to modulate HCV replication.
USP10 affects AR
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USP10 activates AR.
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USP10 activates AR. 10 / 12
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For example, USP10 stimulates AR transcriptional activity in the presence of its synthetic agonist R1881 [67].

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Usp10 is known to enhance AR transcriptional activity [XREF_BIBR, XREF_BIBR] and Usp22 and Usp26 have been found in complexes with AR [XREF_BIBR, XREF_BIBR].

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Overexpression of wild-type USP10 stimulated AR activity as revealed by reporter constructs harbouring selective androgen response elements, non selective steroid response elements or the mouse mammary tumour virus promoter.

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USP10 overexpression enhanced AR transcriptional activity whereas knock-down by specific siRNAs had the opposite effect.

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, confirming that USP10 is a bonafide co-activator of AR regulated transcription.

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Usp10, another DUB reported to target AR, was also shown to enhance AR activity by combining both direct and indirect activity.

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USP10 appeared to modulate AR function.

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Cell based transactivation assays in PC-3/AR cells revealed that overexpression of wild-type USP10, but not of an enzymatically inactive form, stimulated AR activity mediated by reporter constructs harbouring selective androgen response elements (AREs), non selective steroid response elements (SREs) or the mouse mammary tumour virus (MMTV) promoter.

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RNF6 and USP10, which modulate androgen receptor function, showed correlated genomic loss and lower expression in a subset of tumors and gain and higher expression in others.

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The coactivating effects were observed with selective and non selective response elements, indicating that USP10 was a broad coactivator of the AR.
USP10 inhibits AR.
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USP10 inhibits AR. 1 / 3
| 1

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In contrast, the siRNA luciferase screen in LNCaP cells showed that transfection with validated siRNAs targeting USP10 potentiated AR transcriptional activity.
USP10 increases the amount of AR.
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USP10 increases the amount of AR. 1 / 1
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However, it is not clear if inhibition or shRNA knockdown of USP10 lowers AR protein levels.
Spautin-1 affects USP10
1 | 10
1 | 10

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Indeed, a recent study showed that a small molecule, Spautin-1, promoted the degradation of Vps34 by inhibiting two ubiquitin specific proteases USP10 and USP13 that regulate the stability of the Vps34 complex [XREF_BIBR].

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SBI blocks the kinase activity of ULK1, diminishing the phospho regulated capacity of beclin-1 to engage with its binding partners (Egan et al., 2015) and Spautin-1 inhibits the USP10 and USP13 hydrol[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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A previous study reported that Spautin-1 also inhibits USP10 activity XREF_BIBR.

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Spautin-1 inhibits the catalytic activity of both USP10 and USP13 with an IC 50 of ~ 0.6-0.7 microM.

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Molecular analysis revealed that Spautin-1 directly inhibits the activity of the deubiquitinating enzymes (DUBs) ubiquitin specific protease 10 (USP10) and USP13.

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58 Spautin-1 promotes the degradation of BECN1 by inhibiting 2 USPs (ubiquitin-specific peptidases), USP10 and USP13, which target BECN1.

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No evidence text available

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To further determine whether USP10 could be a druggable target in these patients, we evaluated the ex vivo antineoplastic effect of pharmacological inhibition of USP10 by Spautin-1 on primary monocytes from 16 patients with CML.

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Spautin-1 inhibits the activity of the deubiquitinating enzymes USP13 and USP10.

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Spautin-1 inhibits the activity of two ubiquitin specific peptidases, USP10 and USP13, causing an increase in proteasomal degradation of class III PI3 kinase complexes, which have been shown to regulate autophagy [XREF_BIBR].
SIRT6 affects USP10
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SIRT6 activates USP10.
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SIRT6 activates USP10. 8 / 8
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32 These findings present evidence that Sirt6 mediates the effect of USP10 in the regulation of CH in response to Ang II stimulation.

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Ang II induced cardiac hypertrophy potentiated by USP10 knockdown was also completely blocked by Sirt6 activity upregulation.

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Our study has presented evidence that Sirt6 mediates the effect of USP10 in the regulation of CH in response to Ang II stimulation.

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These findings present evidence that Sirt6 mediates the effect of USP10 in the regulation of CH in response to Ang II stimulation.

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These findings demonstrated that the Sirt6 mediated the effect of USP10 in regulation of CH in response to Ang II stimulation.

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Sirt6 Mediates USP10 Regulated Cardiac Hypertrophy.

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To further prove the principle that USP10 suppresses c-Myc transcriptional activity through both SIRT6 and p53, we tested whether knockdown of SIRT6 rescues this USP10 suppressive activity.

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Furthermore, USP10 physically binds to sirtuin 6 (Sirt6) and Sirt6 mediates the effect of USP10 on the regulation of CH.
SIRT6 inhibits USP10.
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SIRT6 inhibits USP10. 1 / 1
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Indeed, knockdown of SIRT6 in p53 +/+ cells partially reversed the suppressive activity of USP10.
SIRT6 increases the amount of USP10.
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SIRT6 increases the amount of USP10. 1 / 1
| 1

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Similarly, knockdown of SIRT6 partially reversed USP10 stable expression mediated tumor suppression in wildtype but not p53-null HCT116 cells.
SIRT6 decreases the amount of USP10.
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SIRT6 decreases the amount of USP10. 1 / 1
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Conversely, Sirt6 deficiency decreased the ameliorative effects of USP10 overexpression in response to HFD treatment.
USP10 affects CFTR
| 10
USP10 decreases the amount of CFTR.
| 5
USP10 decreases the amount of ubiquitinated CFTR. 3 / 3
| 3

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Overexpressing USP-10 decreased the amount of ubiquitinated CFTR and increased its abundance in the plasma membrane of human airway epithelial cells [XREF_BIBR].

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small interference RNA mediated knockdown of USP10 increased the amount of ubiquitinated CFTR and its degradation in lysosomes, and reduced both apical membrane CFTR and CFTR mediated chloride secretion.

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Moreover, a dominant negative USP10 (USP10-C424A) increased the amount of ubiquitinated CFTR and its degradation, whereas overexpression of wt-USP10 decreased the amount of ubiquitinated CFTR and increased the abundance of CFTR.
Modified USP10 decreases the amount of ubiquitinated CFTR. 2 / 2
| 2

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siRNA mediated reduction of USP10 protein expression (by 76 +/-4%, XREF_FIG) increased the amount of ubiquitinated CFTR.

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Moreover, a dominant negative USP10 (USP10-C424A) increased the amount of ubiquitinated CFTR and its degradation, whereas overexpression of wt-USP10 decreased the amount of ubiquitinated CFTR and increased the abundance of CFTR.
USP10 activates CFTR.
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USP10 activates CFTR. 1 / 2
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For example, UCH-L3 localizes to endosomes and regulates the surface levels of ENaC in kidney cells, USP-10 localizes to endosomes and promotes CFTR recycling to the epithelial cell surface, USP20 and USP33 control recycling of beta 2 ARs, and both AMSH and USP8 and UBPY are endosome associated DUBs implicated in regulating EGFR degradation.
Modified USP10 activates CFTR. 1 / 1
| 1

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Moreover, a dominant negative USP10 (USP10-C424A) increased the amount of ubiquitinated CFTR and its degradation, whereas overexpression of wt-USP10 decreased the amount of ubiquitinated CFTR and increased the abundance of CFTR.
USP10 increases the amount of CFTR.
| 2
USP10 increases the amount of ubiquitinated CFTR. 1 / 1
| 1

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Thus, the goal of this study was to test the hypothesis that Cif inhibits USP10, which increases the amount of ubiquitinated CFTR that is degraded in lysosomes, thereby reducing cell and plasma membrane CFTR level.
USP10 increases the amount of CFTR. 1 / 1
| 1

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Thus, the goal of this study was to test the hypothesis that Cif inhibits USP10, which increases the amount of ubiquitinated CFTR that is degraded in lysosomes, thereby reducing cell and plasma membrane CFTR level.
USP10 inhibits CFTR.
| 1
USP10 inhibits ubiquitinated CFTR. 1 / 1
| 1

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Finally, if Cif stabilizes an inhibitory interaction between G3BP1 and USP10, silencing G3BP1 should reduce the Cif induced decrease in USP10 activity as well as the Cif induced increase in ubiquitinated CFTR, and its degradation in lysosomes.
USP10 affects Neoplasms
| 4 3
USP10 inhibits Neoplasms.
| 2 1
| 2 1

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Additionally , USP10 blocks tumor formation via p53 and SIRT6-mediated degradation of c-Myc , thereby stopping cell cycle progression and cancer cell growth [ 53 ] .
| PMC

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For example , in hepatocellular carcinoma , Zhu et al. reported that USP10 promotes proliferation [ 40 ] , whereas Lu et al. found that USP10 suppresses tumor progression by inhibiting mTOR activation [ 41 ] .

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USP10, upon ATM-dependent phosphorylation at threonine 42 and serine 337 residues, is stabilized and translocated to the nucleus to activate p53 through deubiquitinating activity, inducing tumor cell suppression [53].
| PMC
USP10 activates Neoplasms.
| 2 2
| 2 2

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We next found that USP10 coordinately promotes tumor progression with G3BP1.

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For instance, USP10 promotes tumor metastasis through deubiquitination and stabilization of Smad4 in advanced HCC [8].
| PMC

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On the other hand , USP10 , a p53 deubiquitinase , serves as a positive regulator of p53 ; inhibition of USP10 could suppress cancer by degrading oncogenic p53 mutants ( Figure 2b ) [ 32 ] .

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It has been reported that USP10 mediates cancer progression via stabilizing some substrates , such as p53 , STRT6 , AMPK , FLT3 and androgen receptor [ 20-24 ] .
USP10 affects G3BP1
| 4
USP10 inhibits G3BP1.
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USP10 inhibits G3BP1. 2 / 6
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USP10 may prevent G3BP from nucleating SG assembly by locking G3BP in a conformation that influences the NTF2 like domain and mediates or prevents G3BP oligomerization.

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It is also possible that USP10 blocks the helicase function of G3BP, as helicase activity of some proteins, e.g., DDX6 and RCK, has been shown to be required for RNA granule assembly.
USP10 decreases the amount of G3BP1.
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USP10 decreases the amount of G3BP1. 1 / 3
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However, USP10 KD also reduces expression of G3BP1 and G3BP2 (to 58% and 77% of control values, respectively; XREF_FIG), suggesting that the SG inhibition caused by USP10 KD may be caused by reduced levels of G3BP.
USP10 activates G3BP1.
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USP10 activates G3BP1. 1 / 1
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We next found that USP10 coordinately promotes tumor progression with G3BP1.
USP10 affects CD36
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USP10 activates CD36.
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USP10 activates CD36. 5 / 5
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Western blot showed that increased expression of CD36 protein was suppressed by USP10 inhibitor or siRNA ( Figure 4A , 4B ) .

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In this study, our western blotting and RT-qPCR assays revealed that USP10 inhibition promotes the degradation of CD36 protein but does not change its mRNA level.

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USP10 knockdown also inhibited the expression of CD36 protein ( Figure 3C , 3D ) .

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In this study , our western blotting and RT-qPCR assays revealed that USP10 inhibition promotes the degradation of CD36 protein but does not change its mRNA level .

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We found that USP10 inhibitor significantly reduced CD36 expression ( Figure 3E , 3F ) .
USP10 activates ubiquitinated CD36. 2 / 2
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As shown in XREF_FIG, XREF_FIG, USP10 inhibition or knockdown significantly increased ubiquitinated CD36.

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Moreover, the K48-poly-ubiquitinated CD36 was upregulated by Spautin-1 or USP10 siRNA.
USP10 increases the amount of CD36.
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USP10 increases the amount of CD36. 2 / 2
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USP10 knockdown also inhibited the expression of CD36 protein (XREF_FIG, XREF_FIG).

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We found that USP10 inhibition decreased the expression of CD36 in THP1 cells (XREF_FIG).
USP10 decreases the amount of CD36.
| 1
USP10 decreases the amount of CD36. 1 / 1
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We have studied what silencing USP10 induced the inhibition of lipid uptake and CD36 expression.
USP10 affects AMPK
| 1 7
USP10 activates AMPK. 8 / 9
| 1 7

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These results suggest that USP10 deubiquitinase activity is required for its effects in AMPK activation and cellular metabolism.We then explored the mechanism by which USP10 modulates AMPK activation,[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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The fact that USP10 also positively regulates beclin-1 and AMPK would make pharmacologic activators of USP10 particularly effective as autophagy enhancers.

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Only WT USP10, but not the CA mutant could rescue AMPK activation triggered by USP10 RNAi (XREF_FIG), suggesting that USP10 deubiquitinase activity is required for AMPK activation.

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As shown in Figure 4 B, the phosphorylation of USP10 increased significantly after glucose starvation, suggesting that USP10 might be a substrate of AMPK.

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Finally, USP10 deubiquitinates and activates the autophagy-promoting kinase AMPK ( xref ).

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We then explored the mechanism by which USP10 modulates AMPK activation, first by examining whether USP10 directly interacts with AMPK.

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Only WT USP10, but not the CA mutant, could rescue AMPK activation triggered by USP10 RNAi, suggesting that USP10 deubiquitinase activity is required for AMPK activation.

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As shown in XREF_FIG, the phosphorylation of USP10 increased significantly after glucose starvation, suggesting that USP10 might be a substrate of AMPK.
USP10 affects SGs
| 9
USP10 inhibits SGs.
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USP10 inhibits SGs. 5 / 5
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Interestingly, the overexpression of USP10 prevents the formation of SGs by directly binding G3BP via an FGDF motif.

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Cells with an exon 3 deletion may express an FGDF containing inhibitory fragment of USP10, which would suppress SGs as does USP10 1-40 (XREF_FIG) and explain the apparent contradiction.

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Tet induced GFP-USP10 expression prevents AS and CZ induction of SGs (XREF_FIG) but does not alter stress induced polysome disassembly (XREF_FIG), indicating that GFP-USP10 inhibits the cytoplasmic condensation of mRNPs into SGs.

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Here, we have shown that overexpression of EGFP-USP10, but not a mutant lacking an intact FGDF-motif, efficiently blocks the formation of SGs (XREF_FIG).

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When mCherry tagged USP10 is cotransfected with GFP-G3BP1, both proteins colocalize in SGs (XREF_FIG, 4), but mCherry-USP10 coexpressed with GFP-Caprin1 inhibits SGs even upon AS treatment (XREF_FIG, 5 and 6), suggesting that USP10 and Caprin1 compete for limiting G3BP.
USP10 bound to G3BP1 inhibits SGs. 2 / 2
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USP10 lacking the PAM2 motif does not co-IP PABP or eIF4G, but still binds G3BP and blocks SGs (XREF_FIG, 10-12).

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Since the binding of nsP3 and USP10 to G3BP inhibits SGs, we hypothesized that ICP8 binding might do the same.
USP10 activates SGs.
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USP10 activates SGs. 2 / 2
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Rescue experiments using a G3BP1 mutant that lacks the ability to bind Caprin1 or USP10 rescues SGs assembly, whereas other phosphomimetic mutants of G3BP1 (G3BP1-S149E) fail to do that [XREF_BIBR].

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In addition, the overexpression of USP10 without stress stimuli in HT22 cells induced TIA1/Tau/USP10 positive SGs in a deubiquitinase independent manner.
USP10 affects SKP2
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USP10 increases the amount of SKP2.
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USP10 increases the amount of SKP2. 3 / 3
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XREF_FIG, only the knockdown of USP10 and USP13 decreased the expression of SKP2.

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We further explored whether USP10 modulates the expression of SKP2 and thus activating Bcr-Abl in CML cells.

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We further found that only USP10-WT, but not USP10-CA, increased the protein level of SKP2, suggesting that deubiquitinating activity of USP10 is required for SKP2 enrichment.
Modified USP10 increases the amount of SKP2. 2 / 2
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The results showed that overexpression of USP10 increased the protein level of SKP2 in HEK293T and HeLa cells in a manner similar to USP13.

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The result showed that loss of USP10 significantly decreased the expression of SKP2, as well as the phosphorylation and downstream signals of Bcr-Abl, suggesting that USP10 is required for the expression of SKP2 and the phosphorylation of Bcr-Abl in CML cells.
USP10 activates SKP2.
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USP10 activates SKP2. 3 / 3
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Notably, genetic or pharmacological inhibition of USP10 using Spautin-1 prominently decreased the stability of endogenous SKP2 protein, suggesting that USP10 inhibits the degradation of SKP2 in vivo.

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USP10 modulates the SKP2 and Bcr-Abl axis via stabilizing SKP2 in chronic myeloid leukemia.

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Since USP10 is a well characterized DUB in humans, exploring whether USP10 directly regulates the stability of SKP2 protein is attractive.
USP10 decreases the amount of SKP2.
| 1
USP10 decreases the amount of SKP2. 1 / 1
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To our expectation, pharmacological inhibition of USP10 by Spautin-1 significantly increased the poly-ubiquitination level of SKP2.
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However, our results using USP10 functional mutants indicated that ROS inhibition by USP10 is dispensable for USP10 to inhibit apoptosis of HSCs.

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However, our results using USP10 functional mutants indicated that ROS inhibition by USP10 is dispensable for USP10 to inhibit apoptosis of HSCs.

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Upon exposure to an oxidant, USP10 inhibits ROS dependent apoptosis by reducing ROS production.

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Similarly, USP10 and USP13 silencing could induce ROS generation and cause DNA damage.
| PMC

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On exposure to arsenic, an oxidative stress inducer, USP10 is recruited into stress granules (SGs), and USP10 containing SGs reduce reactive oxygen species (ROS) production and inhibit ROS dependent apoptosis.

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USP10-knockout indicated that USP10, through augmenting formation of SGs, reduced reactive oxygen species (ROS) production and inhibited ROS dependent apoptosis.
| PMC

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Since aberrant ROS production has been shown to be a critical apoptosis inducer of HSCs under basal and stress conditions, it was initially assumed that USP10 inhibits apoptosis of HSCs by inhibiting ROS production.

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We showed previously that USP10-KD increases the production of ROS by an oxidant (arsenite).
USP10 affects PTEN
| 2 1 5
USP10 activates PTEN.
| 1 1 3
USP10 activates PTEN. 5 / 5
| 1 1 3

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Specifically , USP10 activates PTEN by preventing its K63-linked polyubiquitination mediated by TRIM25 and suppresses the AKT / mTOR signaling pathway thereby inhibiting NSCLC proliferation , indicating that it may be a potential drug target for cancer treatment .

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The deubiquitinase USP10 restores PTEN activity and inhibits non small cell lung cancer cell proliferation.

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Specifically, USP10 activates PTEN by preventing its K63-linked polyubiquitination mediated by TRIM25 and suppresses the AKT/mTOR signaling pathway thereby inhibiting NSCLC proliferation, indicating that it may be a potential drug target for cancer treatment.

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In contrast to TRIM25, USP10 restored PTEN phosphatase activity and reduced the production of the secondary messenger PI (3,4,5) P3, thereby inhibiting AKT and mTOR pro growth signaling transduction in NSCLC cells.

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Specifically, USP10 activates PTEN by preventing its K63 linked polyubiquitination mediated by TRIM25 and suppresses the AKT and mTOR signaling pathway thereby inhibiting NSCLC proliferation, indicating that it may be a potential drug target for cancer treatment.
USP10 inhibits PTEN.
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USP10 inhibits PTEN. 3 / 3
| 1 2

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Moreover , USP10 , but not its inactive C424A deubiquitinating mutant or other deubiquitinases , abolished PTEN from K63-linked polyubiquitination mediated by TRIM25 .

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Moreover, USP10, but not its inactive C424A deubiquitinating mutant or other deubiquitinases, abolished PTEN from K63 linked polyubiquitination mediated by TRIM25.

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USP10 was reported to inhibit tumor growth and inactivate mTORC1 and AKT signaling by stabilizing AMPKalpha and PTEN in HCC cells.
Cif affects USP10
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Cif inhibits USP10.
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Cif inhibits USP10. 7 / 7
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Cif inhibited ubiquitin specific protease 10 (USP10), a deubiquitinating enzyme, resulting in increased poly-ubiquitination and proteasomal degradation of TAP1.

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Using this assay, we demonstrated that USP10 activity was inhibited 49 +/-4% by Cif (XREF_FIG).

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For example, in this and a previous study we observed that neither USP34, nor USP8 deubiquitinate CFTR, and only USP10 activity was inhibited by Cif XREF_BIBR, XREF_BIBR.

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Cif inactivates USP10 in the early endosome.

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These data are consistent with the view that Cif reduces USP10 activity and thereby increases the amount of multi ubiquitinated CFTR and its degradation in the lysosome.

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If G3BP1 knockdown prevented the Cif mediated inhibition of USP10 activity, we would predict that knockdown of G3BP1 would also eliminate the increase in multi ubiquitinated CFTR and degradation of CFTR induced by Cif.

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The next set of experiments was designed to elucidate how Cif inhibits USP10 activity.
Cif activates USP10.
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Cif activates USP10. 1 / 1
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Current studies are underway to elucidate the mechanism by which the epoxide hydrolase activity of Cif promotes the inactivation of USP10, via enhancement of G3BP1 interaction, leading to the degradation of CFTR.
Quercetin affects USP10
| 7
Quercetin activates USP10.
| 5
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However, Quercetin could also target USP10 for degradation in a proteasome pathway, but not affect GATA-3 level.

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The enhancement of T-bet was inhibited under Quercetin treatment because of the degradation of USP10 by Quercetin.

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Quercetin may target USP10 for degradation and then lead to the destabilization of T-bet.

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We want to know whether Quercetin will modulate USP10.

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We further confirmed Quercetin, a reported inhibitor of T-bet, could target USP10.
Quercetin inhibits USP10.
| 1
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Quercetin treatment downregulated USP10 and promoted T-bet degradation in a proteasome dependent way.
Quercetin decreases the amount of USP10.
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Quercetin decreases the amount of USP10. 1 / 1
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In Human CD4 + T cells, Quercetin treatment also decreased endogenous T-bet and USP10 expression but not GATA-3.
USP10 affects MTOR
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USP10 inhibits MTOR.
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USP10 inhibits MTOR. 4 / 4
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These results suggesting that loss of USP10 can lead to activation of mTOR signaling in vivo.

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Moreover , numerous studies have demonstrated that USP10 inhibited mTOR activation and promoted oncogene-induced senescence to exert a tumor-suppressive effect ( 50 , 51 ) .

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Specifically, USP10 activates PTEN by preventing its K63 linked polyubiquitination mediated by TRIM25 and suppresses the AKT and mTOR signaling pathway thereby inhibiting NSCLC proliferation, indicating that it may be a potential drug target for cancer treatment.

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These results indicate that USP10 may inhibit mTOR activation through regulating PTEN/AKT/PI3K and AMPK signaling pathways in HCC cells.To further dissect how USP10 inhibits mTOR activity, we investig[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
USP10 bound to AMPK_alpha inhibits MTOR. 1 / 1
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Mechanistically, USP10 interacts with and stabilizes PTEN and AMPKalpha by inhibiting their polyubiquitylation, and subsequently suppresses the activity of mTOR signaling pathway.
USP10 bound to PTEN inhibits MTOR. 1 / 1
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Mechanistically, USP10 interacts with and stabilizes PTEN and AMPKalpha by inhibiting their polyubiquitylation, and subsequently suppresses the activity of mTOR signaling pathway.
USP10 activates MTOR.
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USP10 activates MTOR. 2 / 2
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USP10 suppresses tumor progression by inhibiting mTOR activation in hepatocellular carcinoma.

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Taken together, these results revealed that mTOR signaling pathway plays a critical role in USP10 downregulated HCC cells.Next, we investigated whether USP10 mediated stabilization of PTEN and AMPKalp[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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31 Recently , a report suggested that USP10 can inhibit hepatic steatosis , insulin resistance , and inflammation through Sirt6 in nonalcoholic fatty liver disease .

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Ubiquitin Specific Peptidase 10 (USP10) Inhibits Hepatic Steatosis, Insulin Resistance, and Inflammation Through Sirt6.

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31 Recently, a report suggested that USP10 can inhibit hepatic steatosis, insulin resistance, and inflammation through Sirt6 in nonalcoholic fatty liver disease.

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USP10 deletion also promoted inflammatory response in ischemic penumbra of cortical regions by further accelerating nuclear factor kappaB (NF-kappaB) signaling pathway.

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USP10 inhibits hepatic steatosis, insulin resistance and inflammation via Sirt6.

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USP10 overexpression also inhibited while USP10 siRNA enhanced the CNYP induced inhibition of inflammation in ectopic endometrial stromal cells.

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Additionally, USP10 overexpression inhibited hepatocyte inflammation and apoptosis in hepatic I/R injury in vitro and in vivo.
USP10 affects NFkappaB
| 3
USP10 inhibits NFkappaB.
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For example, USP10 can inhibit genotoxic NF-kappaB activation through monocyte chemotactic protein-1-induced protein-1 (MCPIP1)-facilitated deubiquitination of NEMO [XREF_BIBR].

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Suppression of genotoxic NF-kappaB activation by MCPIP1 and USP10.
USP10 activates NFkappaB.
| 1
| 1

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In accordance, depletion of USP10 enhanced NF-kappaB activation induced by IL-1beta or LPS.
USP10 affects HDAC6
| 1 6
USP10 increases the amount of HDAC6.
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USP10 increases the amount of HDAC6. 4 / 4
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Depletion or inhibition of USP10 significantly decreases HDAC6 protein levels, inhibits tumor growth, and increases p53-mutant and null cancer cell sensitivity to cisplatin in a xenograft mouse model.

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XREF_FIG, knockdown of USP10 decreased HDAC6 protein levels as compared to the control H23 cells, while MG132 restored HDAC6 expression in the knockdown cells, indicating that blocking proteasome degradation leads to HDAC6 accumulation.

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XREF_FIG (lanes 1-7), only wild-type USP10, but not the catalytically deficient mutant (USP10 and C424A), significantly increased the endogenous level of HDAC6, indicating that USP10 's deubiquitinase activity is imperative for increasing the protein level of HDAC6.

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The above results suggest that USP10 up-regulates HDAC6 protein expression, most likely through deubiquitinating and consequently stabilizing HDAC6.
USP10 activates HDAC6.
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USP10 activates HDAC6. 3 / 3
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We first hypothesize that in a wild-type p53 background , depletion of USP10 leads to the reduction of HDAC6 as well as affecting an unknown factor , which counteracts the effect of HDAC6 reduction .

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Collectively, these results suggest that USP10 stimulates HDAC6 mediated aggresome inducing activity.

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Overall, our data suggest that USP10 increases HDAC6 protein stability.
USP13 affects USP10
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USP13 deubiquitinates USP10.
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USP13 deubiquitinates USP10. 5 / 5
1 | 4

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Moreover, beclin-1 and USP10 are involved in a potential feedforward mechanism in which beclin-1 stabilizes USP13, which in turn deubiquitinates and stabilizes USP10, leading to increased beclin-1 levels and activity.

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Since USP13 can also deubiquitinate USP10, regulating the stability of USP13 by Beclin1 provides a mechanism for Beclin1 to control the stability of USP10.

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These results suggest that USP13 may directly regulate the deubiquitination of USP10; however, USP10 may regulate USP13 indirectly perhaps by affecting the levels of Vps34 complexes.

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Consistent with this possibility, the ubiquitination levels of USP10 were reduced when cells were cotransfected with an expression vector of USP13 and the addition of spautin-1 inhibited the deubiquitination of USP10 by USP13 (XREF_FIG).
USP13 inhibits USP10.
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USP13 inhibits USP10. 1 / 1
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It will be interesting to elucidate if the stability of the other PI3K and III complex members is also affected, as in the case of Spautin-1 -- mediated inhibition of USP10 and USP13 [XREF_BIBR] and if the control of Beclin 1 stability is mediated by HSP90 in general or whether this represents a regulatory event specifically developed in phagocytic cells.
USP10 affects CH
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USP10 activates CH.
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USP10 activates CH. 5 / 5
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In contrast, cardiac overexpression of USP10 protected against pressure overload induced maladaptive CH.

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Taken together, these results show that USP10 deficiency promotes pressure overload induced CH.

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Taken together, these data indicate that the activation of the Akt/GSK3beta/mTOR/p70-S6K signaling pathways appears to be essential for USP10 mediated CH.

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Because key regulators of CH such as p53, AMPK, and TRAF6 have been reported as downstream targets of USP10, 20, 21 we first evaluated the potential involvement of these target proteins in the CH pathogenesis induced by USP10 deficiency.

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Our observations indicate that USP10 deficiency promotes pressure overload induced CH and alleviated Ang II induced cardiomyocyte enlargement, accompanied by significant decreases in the expression of the fetal genes Anp, Bnp, and Myh7, and vice versa.
USP10 inhibits CH.
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USP10 inhibits CH. 1 / 1
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To determine whether USP10 overexpression could reduce pressure overload induced CH, we also generated cardiac specific USP10 transgenic mice (USP10-TG).
USP10 affects BECN1
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USP10 activates BECN1.
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USP10 activates BECN1. 5 / 5
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Spautin-1 has been recently reported to prevent autophagy by inhibiting the deubiquitinases USP10 and USP13, which leads to beclin 1 and Vps34 (or PI3KIII) degradation [XREF_BIBR].

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XREF_BIBR Spautin-1 promotes the degradation of BECN1 by inhibiting 2 USPs (ubiquitin specific peptidases), USP10 and USP13, which target BECN1.

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The fact that USP10 also positively regulates beclin-1 and AMPK would make pharmacologic activators of USP10 particularly effective as autophagy enhancers.

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Spautin-1, a potent small molecule, can promote the degradation of PI3KCIII and Vps34 complexes by inhibiting two ubiquitin specific peptidases, USP10 and USP13 which target the Beclin-1 subunit of Vp[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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This molecule promotes the degradation of Vps34-PI 3 kinase complexes by inhibiting two ubiquitin specific peptidases, USP10 and USP13, that target the Beclin-1 subunit of Vps34 complexes.
USP10 increases the amount of BECN1.
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USP10 increases the amount of BECN1. 1 / 1
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In addition, USP10 increases the expression of BECN1 and VPS34 proteins.
FOXO4 affects USP10
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FOXO4 increases the amount of USP10.
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FOXO4 increases the amount of USP10. 3 / 3
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In addition, FoxO4 modulated USP10 transcription.

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This study aimed to investigate whether forkhead box O4 (FoxO4) could negatively modulate ubiquitin specific peptidase 10 (USP10) transcription to aggravate the apoptosis and oxidative stress of hypoxia and reoxygenation (H/R)-induced cardiomyocytes through Hippo and YAP pathway.

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In conclusion, FoxO4 negatively modulated USP10 transcription to aggravate the apoptosis and oxidative stress of H/R induced H9C2 cells via blocking Hippo and YAP pathway.
FOXO4 decreases the amount of USP10.
| 1 2
FOXO4 decreases the amount of USP10. 3 / 3
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FoxO4 negatively modulates USP10 transcription to aggravate the apoptosis and oxidative stress of hypoxia and reoxygenation induced cardiomyocytes by regulating the Hippo and YAP pathway.

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FoxO4 negatively modulates USP10 transcription to aggravate the apoptosis and oxidative stress of hypoxia/reoxygenation-induced cardiomyocytes by regulating the Hippo/YAP pathway.

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FoxO4 overexpression could reverse the protective effects of USP10 overexpression on H/R induced H9C2 cells by regulating the Hippo and YAP signaling pathway.
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Pirinixic acid increases the amount of USP10.
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Pirinixic acid increases the amount of USP10. 4 / 4
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Pirinixic acid decreases the amount of USP10.
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Pirinixic acid decreases the amount of USP10. 1 / 1
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Pirinixic acid activates USP10.
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USP10 affects G3BP2
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USP10 inhibits G3BP2.
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USP10 inhibits G3BP2. 1 / 3
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GFP-USP10 overexpression inhibits B-isox precipitation of G3BP2 (XREF_FIG, lanes 4-6 vs. 1-3) and modestly decreases that of G3BP1 and Caprin1, whereas that of TIAR is unchanged.
USP10 decreases the amount of G3BP2.
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USP10 decreases the amount of G3BP2. 2 / 2
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However, USP10 KD also reduces expression of G3BP1 and G3BP2 (to 58% and 77% of control values, respectively; XREF_FIG), suggesting that the SG inhibition caused by USP10 KD may be caused by reduced levels of G3BP.

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USP10 regulates androgen mediated signalling and inhibits p53 activities by regulating G3BP2 expression.
USP10 increases the amount of G3BP2.
| 1
Modified USP10 increases the amount of G3BP2. 1 / 1
| 1

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Expression of GFP-USP10 (lanes 4-6 and 16-18) increases G3BP2 expression (XREF_FIG, lanes 10-12 vs. 7-9), but the increased G3BP2 is not precipitated by B-isox (lanes 4-6), suggesting that B-isox binds and/or precipitates a SG-competent form of G3BP that is rendered SG-incompetent and B-isox soluble upon USP10 binding.
BECN1 affects USP10
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BECN1 activates USP10.
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BECN1 activates USP10. 4 / 4
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Another interesting observation made in the Spautin-1 study is that knock-down of VPS34 and Beclin 1 causes instability of USP10 and USP13, which indicates the existence of a regulatory feedback loop [XREF_BIBR].

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USP10 is a de-ubiquitinating enzyme that promotes accumulation of p53, so Beclin1 mediates down-regulation of USP10 and reduces p53 levels [XREF_BIBR].

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The close functional interconnection between the central PI3K-III subunits and the DUBs is demonstrated by the interesting observation that knock-down of VPS34 and Beclin 1 causes instability of USP10 and USP13, which strongly indicates the existence of a regulatory feedback loop [XREF_BIBR].

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Taken together, these results suggest that Beclin1 is the primary target of USP10 and USP13.
BECN1 inhibits USP10.
| 1
BECN1 inhibits USP10. 1 / 1
| 1

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It is interesting to note that the knock-down of VPS34 and BECLIN 1 also causes the degradation of USP10 and USP13, which indicates the existence of a regulatory feedback loop [XREF_BIBR].
BECN1 increases the amount of USP10.
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BECN1 increases the amount of USP10. 1 / 1
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Unexpectedly, we found that the knockdown of Beclin1 or Vps34 could also reduce the endogenous levels of USP10 and USP13 (XREF_FIG).
USP10 affects CDKN1A
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USP10 activates CDKN1A.
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USP10 activates CDKN1A. 2 / 3
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As shown in XREF_FIG, overexpression of WT USP10 increased p21 promoter activity in HCT116 p53 +/+ cells, but not in HCT116 p53 -/- cells.

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Stable knockdown of USP10 by shRNA inhibited p21 promoter activity in HCT116 p53 +/+ cells, but had little effect in HCT116 p53 -/- cells (XREF_FIG).
USP10 inhibits CDKN1A.
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USP10 inhibits CDKN1A. 1 / 1
| 1

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Usp10 overexpression abolished the estrogen mediated regulation of p53 and the downstream transcriptional gene p21.
USP10 increases the amount of CDKN1A.
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USP10 increases the amount of CDKN1A. 1 / 1
| 1

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Reconstitution of USP10 in CAKI-1 and CAKI-2 (WT p53 cell lines) restored p53 expression and increased p21 and BAX expression (XREF_SUPPLEMENTARY).
USP10 decreases the amount of CDKN1A.
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USP10 decreases the amount of CDKN1A. 1 / 1
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Interestingly, downregulation of USP10 significantly decreased p53 stabilization and the expression of p53 target genes p21 and Bax after DNA damage (XREF_FIG).
TP53 affects USP10
| 6
TP53 decreases the amount of USP10.
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Mutated TP53 decreases the amount of USP10. 1 / 1
| 1

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Since very low percentage of RCC cases are found to have p53 mutations and IARC p53 Database : www.IARC.fr/p53/index.html), decreased expression of USP10 could be another mechanism to inhibit p53 function in RCC.
TP53 decreases the amount of USP10. 1 / 1
| 1

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Since very low percentage of RCC cases are found to have p53 mutations and IARC p53 Database : www.IARC.fr/p53/index.html), decreased expression of USP10 could be another mechanism to inhibit p53 function in RCC.
Modified TP53 decreases the amount of USP10. 1 / 1
| 1

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Loss of p53 partially abrogated the suppressive activity of USP10 overexpression in tumor formation because the average tumor weights from the USP10 expression p53-null HCT116 cells were 0.7 g comparing to 0.3 g by USP10 expressed p53 +/+ HCT116 cells.
TP53 activates USP10.
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TP53 activates USP10. 2 / 2
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Since USP10 mediates the deubiquitination of p53, regulation of the deubiquitination activity of USP10 by Beclin1 likely plays an important role in tumor suppression.

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Downregulation of p53 abolished the inhibitory effect of USP10 on tumor growth (XREF_FIG and data not shown), confirming that USP10 inhibits cancer cell growth by stabilizing p53.
TP53 inhibits USP10.
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TP53 inhibits USP10. 1 / 1
| 1

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Furthermore, USP10 knockdown mediated cell cycle progression was partially rescued by either SIRT6 or p53 co-expression.
USP10 affects Proteasome
| 4
| 4

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Based on USP10 induced ubiquitinated protein aggregation, we hypothesized that coexpression of USP10 with an aggregation-prone protein inhibits proteasome activity.

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Thus, USP10 and p62 might inhibit proteasome activity by trapping proteasome components in protein aggregates and/or aggresomes.

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These results suggested that coexpression of USP10 with an aggregation-prone protein inhibits proteasome activity to increase the amount of insoluble ubiquitinated proteins, thereby augmenting aggresome formation.

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Moreover, a proteasome activity reporter YFP-CL1 indicated that USP10 together with YFP-CL1 inhibits proteasome activity (XREF_FIG F).
USP10 affects USP10
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USP10 activates USP10.
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USP10 activates USP10. 3 / 4
| 3

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Together, these results suggested that AMPK phosphorylates USP10 at S76, which activates USP10 and facilitates further activation of AMPK under energy stress, forming a feedforward loop.Given the impo[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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Together, these results suggested that AMPK phosphorylates USP10 at S76, which activates USP10 and facilitates further activation of AMPK under energy stress, forming a feedforward loop.

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These results suggest that S76 phosphorylation of USP10 increases the deubiquitinase activity of USP10.
USP10 decreases the amount of USP10.
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USP10 decreases the amount of USP10. 1 / 1
| 1

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To exclude the probable off-target effects, two more pairs of USP10 shRNAs were used to knockdown the expression of USP10.
| 1 3

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For example , USP10 inhibits lung cancer cell growth and invasion .

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USP10 inhibits lung cancer cell growth and invasion by upregulating PTEN.

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For example, USP10 inhibits lung cancer cell growth and invasion.

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Moreover, USP10 inhibited cell growth and invasion in lung cancer [XREF_BIBR], and was an independent factor for the prognosis of gastric carcinoma [XREF_BIBR].
| PMC
| 1

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In the current study, we found that there was no correlation between expression of TM4SF1 and USP10, S100A12, p53, or Ki67 expression in GC, suggesting that TM4SF1 plays a distinct role in GC invasion and metastasis from those of USP10, S100A12, p53, or Ki67, although they all contribute to cancer invasion and metastasis.
USP10 affects SQSTM1
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USP10 increases the amount of SQSTM1.
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Modified USP10 increases the amount of SQSTM1. 2 / 2
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Moreover, USP10 expression increased the amount of insoluble p62 in p62 wild-type cells (XREF_FIG B).

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USP10 overexpression without MG-132 treatment increased the amounts of p62 and insoluble ubiquitinated proteins (XREF_FIG B), whereas USP10-KD cells treated with MG-132 increased the amounts of p62 and ubiquitinated proteins more than USP10-WT cells (XREF_FIG E).
USP10 activates SQSTM1.
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USP10 activates SQSTM1. 2 / 2
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In addition to USP10-WT, USP10 96-798, but not USP10 1-116, increased the size of p62 aggregates and aggresomes (XREF_FIG E and 5F).

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These results suggested that USP10 functions to stimulate transport of p62 aggregates to the perinuclear aggresome formation site.
USP10 inhibits SQSTM1.
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USP10 inhibits SQSTM1. 1 / 1
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These results indicated that USP10 and p62 cooperatively inhibit MG-132-induced cell death by promoting the formation of aggresomes and p62 aggregates.
PIK3C3 affects USP10
| 5
PIK3C3 inhibits USP10.
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PIK3C3 inhibits USP10. 2 / 2
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It is interesting to note that the knock-down of VPS34 and BECLIN 1 also causes the degradation of USP10 and USP13, which indicates the existence of a regulatory feedback loop [XREF_BIBR].

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Using an imaging-based screen, Liu et al. (2011) recently identified a highly potent small molecule inhibitor of autophagy they named spautin-1 (specific and potent autophagy inhibitor 1), which promotes degradation of the Vps34 complexes via inhibiting ubiquitin-specific processing protease 10 (USP10) and USP13, two ubiquitin-specific peptidases that target the deubiquitination of Beclin1.2.
PIK3C3 activates USP10.
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PIK3C3 activates USP10. 2 / 2
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Another interesting observation made in the Spautin-1 study is that knock-down of VPS34 and Beclin 1 causes instability of USP10 and USP13, which indicates the existence of a regulatory feedback loop [XREF_BIBR].

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The close functional interconnection between the central PI3K-III subunits and the DUBs is demonstrated by the interesting observation that knock-down of VPS34 and Beclin 1 causes instability of USP10 and USP13, which strongly indicates the existence of a regulatory feedback loop [XREF_BIBR].
PIK3C3 increases the amount of USP10.
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PIK3C3 increases the amount of USP10. 1 / 1
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Unexpectedly, we found that the knockdown of Beclin1 or Vps34 could also reduce the endogenous levels of USP10 and USP13 (XREF_FIG).

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Thus, the goal of this study was to test the hypothesis that Cif inhibits USP10, which increases the amount of ubiquitinated CFTR that is degraded in lysosomes, thereby reducing cell and plasma membrane CFTR level.

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To provide additional support for the hypothesis that Cif inactivation of USP10 is responsible for the increase in the amount of ubiquitinated CFTR and its lysosomal degradation, we examined the amount of multi-ubiquitinated CFTR following siRNA knockdown of USP10.

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Specifically, Cif inhibits the deubiquinating enzyme ubiquitin specific peptidase 10 (USP10), thereby reducing the USP10-mediated deubiquination of CFTR and promoting CFTR trafficking to and degradation in lysosomes [87].
| PMC

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Cif inactivates USP10 in the early endosome.

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NLRP7 or USP10 knockdown dramatically inhibited liver metastasis in a mouse model.

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Targeting USP10 by shRNA inhibited CRC proliferation and metastasis, and this effect was reversed by overexpression of NLRP7.

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In the current study, we found that there was no correlation between expression of TM4SF1 and USP10, S100A12, p53, or Ki67 expression in GC, suggesting that TM4SF1 plays a distinct role in GC invasion and metastasis from those of USP10, S100A12, p53, or Ki67, although they all contribute to cancer invasion and metastasis.

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For instance, USP10 promotes tumor metastasis through deubiquitination and stabilization of Smad4 in advanced HCC [8].
| PMC
USP10 affects FLT3
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USP10 activates FLT3. 4 / 4
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USP10 inhibition leads to death of cells driven by active SYK or oncogenic FLT3 and potentiates the anti-leukemic effects of FLT3 inhibition in these cells.

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Inhibition of USP10 induces degradation of oncogenic FLT3.

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Intriguingly, USP10 inhibition has been shown to promote oncoprotein FLT3 degradation, suggesting that USP10 could be considered as a potential pharmacological target for fighting FLT3- mutant AML disease [XREF_BIBR].

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In addition, we show that USP10 inhibition potentiates the effects of FLT3 inhibition in cells driven by activated SYK.
USP10 affects SYK
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USP10 activates SYK.
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USP10 activates SYK. 3 / 3
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14 Yang et al. provide compelling evidence that SYK can be degraded by inhibition of USP10 leading to cell death in AML cells driven by activated SYK or mutant FLT3.

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The use of USP10 inhibition to degrade SYK may additionally be explored as a potential treatment approach for other malignancies for which SYK plays an important role.

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Inhibition of the deubiquitinase USP10 induces degradation of SYK.
USP10 increases the amount of SYK.
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USP10 increases the amount of SYK. 1 / 1
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To further establish whether loss of USP10 leads to loss of SYK at the level of protein and is not due to suppression of transcription, we first analysed the half-life of SYK in USP10 KD versus SCR KD control MOLM14 cells and found USP10 KD to considerably shorten the half-life of SYK.
USP10 affects MDM2
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USP10 inhibits MDM2.
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USP10 inhibits MDM2. 1 / 2
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25 As a tumour suppressor gene, USP10 was found to reverse the effect of Mdm2 on the exocytosis and degradation of p53.
USP10 activates MDM2.
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USP10 activates MDM2. 2 / 2
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However, coexpression of USP10 or HAUSP, but not USP10 CA or USP10Delta1-100, significantly reversed the inhibitory effect of Mdm2 on p53 mediated apoptosis.

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In contrast to USP7 and USP2a, USP10 specifically deubiquitinate p53 because knockdown of USP10 in HCT116 p53-/- cells does not cause Mdm2 reduction [XREF_BIBR].
| 4
USP10 activates Cell Survival.
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The MTS results also showed that pharmacological inhibition of USP10 with Spautin-1 notably decreased the cell viability of CML cells.

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Thus, USP10 and p62 promote cell survival by reducing the amount of cytotoxic ubiquitinated protein monomers and oligomers.

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Furthermore, depletion of USP10 in lung cancer cells causes decreased apoptosis and increased cell survival upon treatment with DNA damaging agents.
USP10 inhibits Cell Survival.
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Biologically, silenced USP10 in lung cancer cells contributes to the elongated cell survival and depressed apoptosis, partially through deubiquitinating the mismatch repair protein MSH2 [XREF_BIBR], or negatively modulating EIF4G1 mediated functions [XREF_BIBR].
USP10 affects AKT
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USP10 inhibits AKT.
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USP10 inhibits AKT. 2 / 2
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USP10 was reported to inhibit tumor growth and inactivate mTORC1 and AKT signaling by stabilizing AMPKalpha and PTEN in HCC cells.

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Specifically, USP10 activates PTEN by preventing its K63 linked polyubiquitination mediated by TRIM25 and suppresses the AKT and mTOR signaling pathway thereby inhibiting NSCLC proliferation, indicating that it may be a potential drug target for cancer treatment.
Modified USP10 inhibits AKT. 1 / 1
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The results showed that overexpression of wild-type USP10 promoted the deubiquitination of Sirt6 and inhibited the activation of downstream Akt signaling pathway, while mutant USP10 lost this function.
USP10 decreases the amount of AKT.
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USP10 decreases the amount of AKT. 1 / 1
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As anticipated, overexpressing USP10 markedly inhibited the expression of P-AKT and P-S6, and increases P-AMPKalpha expression in vivo.
Vasopressin affects USP10
| 3
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In mCCD (cl1) cells, vasopressin increases SNX3 protein but not mRNA, supporting the idea that the vasopressin induced Usp10 deubiquitylates and stabilizes endogenous SNX3 and consequently promotes cell surface expression of ENaC.

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For example, vasopressin can induce USP10 (ubiquitin specific protease) in mouse cortical collecting duct cells and its interaction with USP10 deubiquitinates sorting nexin 3 results in stabilization [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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We have identified a mRNA encoding the deubiquitylating enzyme ubiquitin specific protease 10 (Usp10), whose expression is increased by vasopressin at both the mRNA and the protein level.
USP10 affects INS
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USP10 inhibits INS. 3 / 3
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Ubiquitin Specific Peptidase 10 (USP10) Inhibits Hepatic Steatosis, Insulin Resistance, and Inflammation Through Sirt6.

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31 Recently, a report suggested that USP10 can inhibit hepatic steatosis, insulin resistance, and inflammation through Sirt6 in nonalcoholic fatty liver disease.

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USP10 inhibits hepatic steatosis, insulin resistance and inflammation via Sirt6.
USP10 affects Histone
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USP10 activates Histone. 3 / 3
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To test whether USP10 targets histones as substrates, we co-expressed Flag tagged USP10 (Flag-USP10) with tagged H2A.Z or H2A in 293T cells and measured the levels of ubiquitylated histones by Western blot.

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Supporting our finding that USP10 targets histones, cells with stable knockdown of USP10 consistently have higher levels of H2A.Zub1 and H2Aub1, whereas the levels of H2Bub1 remain unchanged (XREF_FIG D).

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Importantly, increased USP10 expression did not affect the levels of endogenous H2Bub1 (XREF_FIG B), indicating that USP10 specifically targets the H2A family of histones.
USP10 affects Foam Cells
| 3
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Significantly , USP10 promotes foam cell formation .

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What is more , the formation of foam cell is inhibited by USP10 inhibitor or siRNA in RAW264.7 and THP1 cells .

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USP10 inhibition or deletion diminishes the formation of foam cell .
USP10 affects FUT1
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USP10 inhibits FUT1. 3 / 3
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These results suggest that inhibition of HSC apoptosis is a function of USP10 to maintain the number of HSCs in FL, and that USP10 selectively inhibits apoptosis of HSCs, MPPs, and HPCs but not more differentiated LCPs.

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However, our results using USP10 functional mutants indicated that ROS inhibition by USP10 is dispensable for USP10 to inhibit apoptosis of HSCs.

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Since aberrant ROS production has been shown to be a critical apoptosis inducer of HSCs under basal and stress conditions ( xref ), it was initially assumed that USP10 inhibits apoptosis of HSCs by inhibiting ROS production.
USP10 affects FOXO4
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USP10 increases the amount of FOXO4. 3 / 3
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In addition, FoxO4 modulated USP10 transcription.

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In conclusion, FoxO4 negatively modulated USP10 transcription to aggravate the apoptosis and oxidative stress of H/R induced H9C2 cells via blocking Hippo and YAP pathway.

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FoxO4 negatively modulates USP10 transcription to aggravate the apoptosis and oxidative stress of hypoxia and reoxygenation induced cardiomyocytes by regulating the Hippo and YAP pathway.
AMPK affects USP10
| 1 2
AMPK activates USP10. 3 / 3
| 1 2

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After AMPK is partially activated, AMPK activates USP10 to remove the inhibitory ubiquitination on itself, forming a positive feedforward loop.

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In this thorough study, AMPK was also shown to activate USP10 via phosphorylation of S76, indicating the presence of a positive feedforward loop important for maintenance of metabolic homeostasis in liver.

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After AMPK is partially activated, AMPK activates USP10 to remove the inhibitory ubiquitination on itself, forming a positive feedforward loop.
Bisphenol A affects USP10
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Bisphenol A increases the amount of USP10.
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Bisphenol A increases the amount of USP10. 2 / 2
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Bisphenol A decreases the amount of USP10.
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Bisphenol A decreases the amount of USP10. 1 / 1
1 |

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USP10 affects autophagy
| 1 2
USP10 inhibits autophagy.
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These results suggested that LC3 is degraded by autophagy in both USP10-WT and USP10-KD cells with or withoutMG-132 treatment, and that USP10-KD does not inhibit autophagy mediated degradation of LC3.

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Because the reductions in the levels of USP10 and USP13 in H4-LC3-GFP cells treated with spautin-1 appeared later than the reductions in the levels of Vps34 complexes and autophagy (XREF_FIG), the reduced levels of USP10 and USP13 are unlikely to be the primary reason for the ability of spautin-1 to reduce the levels of PtdIns3P and inhibit autophagy.
USP10 activates autophagy.
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USP10 has also been shown to enhance autophagy by deubiquitinating beclin-1 , a component of class-III PI3K complexes that catalyze the formation of phosphatidylinositol 3-phosphate at both autophagy initiation and autophagosome maturation steps ( 21 ) .
USP10 affects DNA Damage
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USP10 activates DNA Damage.
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We identify 9 direct binding partners of p53 in the nuclear RNA interactome, including USP10, which deubiquitinates and activates p53 in response to DNA damage, and Sumo1, which can itself become covalently coupled to p53 to regulate its activity and subcellular localization (XREF_SUPPLEMENTARY) XREF_BIBR XREF_BIBR XREF_BIBR.
USP10 inhibits DNA Damage.
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Similarly, USP10 and USP13 silencing could induce ROS generation and cause DNA damage.
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FSTL1 affects USP10
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FSTL1 activates USP10.
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FSTL1 activates USP10. 2 / 2
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Further in vitro analysis provided evidence that FSTL1 activated USP10/Notch1 signaling to inhibit myocardial fibrosis.
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The present study revealed that FSTL1 and USP10 were significantly activated in T2DM mice with MI, and FSTL1 treatment further increased USP10 activation and alleviating cardiac dysfunction by reducing myocardial fibrosis.
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FSTL1 increases the amount of USP10.
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FSTL1 increases the amount of USP10. 1 / 1
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Simultaneously, the data in Figure 5 revealed that the expression of Notch1 and USP10 were elevated in cardiac tissue post MI in T2DM, and further activated by FSTL1 administration.
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Tetrachloromethane increases the amount of USP10. 2 / 2
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Resveratrol affects USP10
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As expected, the interaction between G3BP1 and USP10 decreased in HCT116 cells treated with resveratrol (XREF_FIG).
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Treatment of cells with LMB induced USP10 accumulation in the nucleus, suggesting that USP10 is actively exported out of nucleus in unstressed cells.

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LMB treatment also induced USP10 nuclear localization, suggesting that USP10 is actively exported out of the nuclear in unstressed cells.
Indometacin affects USP10
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Indometacin decreases the amount of USP10. 2 / 2
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Vehicle Emissions increases the amount of USP10. 2 / 2
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USP7 affects USP10
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USP7 inhibits USP10. 2 / 2
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Weisberg et al. have performed a phenotypic screen and identified compounds originally discovered for USP7 that inhibit USP10 and induce degradation of the oncogenic kinase FLT3 [ 42 ] .

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Weisberg et al. have performed a phenotypic screen and identified compounds originally discovered for USP7 that inhibit USP10 and induce degradation of the oncogenic kinase FLT3 [ xref ].
USP10 affects tioguanine
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When we planned to continue our 2016 study 41, we noticed that USP10 only promotes sensitivity to 6-TG in A549, a wild-type p53 cell line, but not in H1299, a null-p53 cell line.

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However, it seems to contradict the finding that USP10 promotes sensitivity to 6-TG by stabilizing MSH2 41.
| 2
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USP10 modulates anterograde and retrograde vesicular trafficking, the localization and stability of p53 and binds Dengue virus RNA.

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Usp10 inhibition attenuated H 2 O 2 -induced senescence in MLO-Y4 cells, as indicated by p53 and p21 quantification, a senescence associated beta-galactosidase (SA-beta-gal) assay, and p53 localization visualization with a confocal microscope.
USP10 affects lactate
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USP10 activates lactate. 2 / 2
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Expression of USP10 shRNA increased lipid droplet content, lactate production and glycolytic gene expression in control cells but not in AMPKalpha deficient cells (XREF_SUPPLEMENTARY), indicating that USP10 regulates cellular metabolism through AMPK.

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Expression of USP10 shRNA increased lipid droplet content, lactate production, and glycolytic gene expression in control cells but not in AMPKalpha deficient cells, indicating that USP10 regulates cel[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
USP10 affects glucose
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Furthermore, Usp10 knockout mice showed increased blood glucose level and decreased glucose infusion rate (XREF_FIG), indicating USP10 regulates hepatic glucose metabolism.

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Furthermore, Usp10 knockout mice showed increased blood glucose level and decreased glucose infusion rate, indicating USP10 regulates hepatic glucose metabolism.
USP10 affects cholesterol
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Knockout of Usp10 significantly increased hepatic triglyceride and cholesterol contents, as measured by a colorimetric assay and HE staining under both normal fat diet and high fat diet condition (XREF_FIG).

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Knockout of Usp10 significantly increased hepatic triglyceride and cholesterol contents, as measured by a colorimetric assay and H&E staining under both normal-fat diet and high-fat diet conditions.
USP10 affects cell cycle
| 2
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Furthermore, USP10 knockdown mediated cell cycle progression was partially rescued by either SIRT6 or p53 co-expression.

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Third, USP10 antagonizes c-Myc transcriptional activity and cell cycle progression through both SIRT6 and p53.
USP10 affects Ubiquitin
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We found that ubiquitin specific peptidase 10 (USP10) interacted with the NOTCH1 intracellular domain (NICD1) to slow the ubiquitin dependent turnover of this short lived form of the activated NOTCH1 receptor.

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Silencing of the DUB USP10 induces a buildup of ubiquitin on integrins beta1 and beta5 in cell lysates, whereas recombinant USP10 removes ubiquitin from these integrin subunits.
USP10 affects Phosphatase
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In contrast to TRIM25, USP10 restored PTEN phosphatase activity and reduced the production of the secondary messenger PI (3,4,5) P3, thereby inhibiting AKT and mTOR pro growth signaling transduction in NSCLC cells.

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In contrast to TRIM25 , USP10 restored PTEN phosphatase activity and reduced the production of the secondary messenger PI ( 3,4,5 ) P3 , thereby inhibiting AKT / mTOR pro-growth signaling transduction in NSCLC cells .
USP10 affects Notch
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USP10 inhibits Notch. 2 / 2
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Inactivation of USP10 can diminish Notch induced target gene expression in endothelial cells.

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Accordingly, inactivation of USP10 reduced NICD1 abundance and stability and diminished Notch induced target gene expression in ECs.
USP10 affects MSI2
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USP10 increases the amount of MSI2. 2 / 2
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XREF_BIBR In colon cancer, USP10 positively regulates the expression of MSI2 by de-ubiquitination.

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We investigated whether USP10 positively regulates the expression of MSI2 by deubiquitination and confirmed the type of polyubiquitin chain that is linked to MSI2.
USP10 affects MSH2
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USP10 activates MSH2. 2 / 2
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However, it seems to contradict the finding that USP10 promotes sensitivity to 6-TG by stabilizing MSH2 41.

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So, HDAC6 and USP10 exert opposing effect on MSH2 : HDAC6 promotes degradation of MSH2, while USP10 promotes stabilization of MSH2.

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It has been demonstrated that USP10 inhibits hepatic steatosis and insulin resistance via Sirt6 , in which Sirt6 represses the transcription levels of SREBP1 / SREBP2 and their target genes [ 114 ] .

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31 Recently , a report suggested that USP10 can inhibit hepatic steatosis , insulin resistance , and inflammation through Sirt6 in nonalcoholic fatty liver disease .
USP10 affects HSP90
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USP10 inhibits HSP90. 2 / 2
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USP10 inhibits cytokine deprivation-induced apoptosis of HSPCs in vitro, and this inhibition requires the deubiquitinase activity of USP10.

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These results suggest that USP10 inhibits apoptosis of HSPCs by deubiquitinating molecule(s) other than the ones analyzed here.
USP10 affects CRC
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USP10 activates CRC. 2 / 2
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USP10 accelerates the CRC malignant process by upregulating NLRP7.

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Targeting USP10 by shRNA inhibited CRC proliferation and metastasis, and this effect was reversed by overexpression of NLRP7.

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Overexpression of USP10 enhanced the R1881 dependent response of all three tested minimal promoters, but had no significant effects on the unstimulated activity.

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For example, USP10 stimulates AR transcriptional activity in the presence of its synthetic agonist R1881 [67].
Particulate Matter increases the amount of USP10. 2 / 2
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Histone affects USP10
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Histone activates USP10. 2 / 2
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To test whether USP10 targets histones as substrates, we co-expressed Flag tagged USP10 (Flag-USP10) with tagged H2A.Z or H2A in 293T cells and measured the levels of ubiquitylated histones by Western blot.

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Supporting our finding that USP10 targets histones, cells with stable knockdown of USP10 consistently have higher levels of H2A.Zub1 and H2Aub1, whereas the levels of H2Bub1 remain unchanged (XREF_FIG D).
DCN affects USP10
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DCN activates USP10. 2 / 2
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As ubiqutin signaling serves as an early harbinger of autophagy, decorin might augment the USP10 activity (or generally modulate ubiquitin signaling in favor of autophagy) for increased Beclin 1 or Peg3 stability.

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As ubiqutin signaling serves as an early harbinger of autophagy, decorin might augment the USP10 activity (or generally modulate ubiquitin signaling in favor of autophagy) for increased Beclin 1 or Peg3 stability.
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Benzo[a]pyrene increases the amount of USP10.
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Benzo[a]pyrene increases the amount of USP10. 1 / 1
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Benzo[a]pyrene activates USP10.
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To identify the E3 ubiquitin ligase that mediates BaP induced ACE2 degradation, the expression of several critical E3 ligases, e.g., the F-box (40 amino acid motif)-containing E3 ligase S-phase kinase associated protein 2 (Skp2), beta-transducin repeat containing E3 ubiquitin protein ligase (beta-TRCP), the nuclear interaction partner of ALK (NIPA), the RING finger and WD repeat domain 3 (RFWD3), and deubiquitinase ubiquitin specific protease 10 (USP10) were tested in cells treated with BaP.
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ZC3H12A affects USP10
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ZC3H12A deubiquitinates USP10.
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ZC3H12A leads to the deubiquitination of USP10. 1 / 1
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Two N-terminal domains of MCPIP1 are essential for MCPIP1 to direct USP10 dependent deubiquitination.
ZC3H12A activates USP10.
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ZC3H12A activates USP10. 1 / 1
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[XREF_BIBR] Further investigation revealed that MCPIP1, although itself lacks DUB activity, could serve as an adaptor protein to enhance interaction of deubiquitinase USP10 with polyubiquitinated NEMO, which in turn removes the linear ubiquitin chains from NEMO and suppresses NF-kappaB signaling upon DNA damage.
| 2
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We then asked whether the PAM2 motif contributes to USP10 mediated SG inhibition.
USP10 activates seaborgium atom.
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For example, the expression of the catalytically-inactive USP10 was able to only partially rescue the SG defects observed in USP10 deficient MEFs.
USP10 affects dioxygen
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USP10 inhibits dioxygen.
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Upon exposure to an oxidant, USP10 reduces production of reactive oxygen species (ROS), thereby inhibiting ROS dependent apoptosis.
USP10 activates dioxygen.
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USP10 also has deubiquitinase independent functions, such that USP10 inhibits apoptosis by reducing reactive oxygen species (ROS) production induced by an oxidative stress inducer arsenite.
USP10 affects TBP
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USP10 increases the amount of TBP.
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Modified USP10 increases the amount of TBP. 1 / 1
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We then examined whether increasing USP10 protein levels in post mitotic myotubes can rescue TBP protein levels.
USP10 activates TBP.
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USP10 activates TBP. 1 / 1
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Moreover, cycloheximide chase experiments (CHX) revealed that USP10 overexpression increased TBP protein half-life in C2C12 myoblasts (XREF_FIG).
USP10 affects SNCA
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USP10 increases the amount of SNCA.
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Modified USP10 increases the amount of SNCA. 1 / 1
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Like CFTR-DeltaF508, coexpression of USP10 with GFP-alpha-synuclein and synphilin-1 increased the amounts of insoluble alpha-synuclein and insoluble ubiquitinated proteins (XREF_FIG D).
USP10 activates SNCA.
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USP10 activates SNCA. 1 / 1
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USP10 induced aggresomes containing alpha-synuclein, a pathogenic protein in Parkinson disease, in cultured cells.
USP10 affects SNAI2
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USP10 increases the amount of SNAI2.
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USP10 increases the amount of SNAI2. 1 / 1
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Genetic knockdown of USP10 leads to suppressed Slug levels with a decreased expression of the mesenchymal marker Vimentin.
USP10 decreases the amount of SNAI2.
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Modified USP10 decreases the amount of SNAI2. 1 / 1
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Reversely, overexpression of USP10 elevates the level of both Slug and Vimentin.
USP10 affects PIK3C3
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USP10 increases the amount of PIK3C3.
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USP10 increases the amount of PIK3C3. 1 / 1
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In addition, USP10 increases the expression of BECN1 and VPS34 proteins.
USP10 activates PIK3C3.
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USP10 activates PIK3C3. 1 / 1
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We propose that USP10 and USP13 mediate the deubiqutination of Vps34 complexes to regulate the levels of class III PI3 kinase.
USP10 affects NPPA
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USP10 decreases the amount of NPPA. 1 / 1
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Compared with AdGFP transfection, AdUSP10 notably alleviated Ang II induced cardiomyocyte enlargement, accompanied by significant decreases in the expression of the fetal genes Anp, Bnp, and Myh7; in contrast, USP10 silencing significantly exacerbated myocyte hypertrophy and upregulated the expression of Anp, Bnp, and Myh7 compared with that in primary cells infected with AdshRNA, suggesting that USP10 can directly mitigate the hypertrophic growth of isolated myocytes induced by Ang II.
Modified USP10 decreases the amount of NPPA. 1 / 1
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Furthermore, overexpression of wild-type USP10 inhibits cardiomyocyte enlargement and the expression of ANP, BNP, and Myh7, whereas overexpression of mutant USP10 eliminated this effect.
USP10 affects NLRP7
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USP10 increases the amount of NLRP7.
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USP10 increases the amount of NLRP7. 1 / 1
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USP10 upregulation increased NLRP7 protein levels.
USP10 activates NLRP7.
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USP10 activates NLRP7. 1 / 1
| 1

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USP10 accelerates the CRC malignant process by upregulating NLRP7.
USP10 affects KLF4
| 2
USP10 inhibits KLF4.
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USP10 inhibits KLF4. 1 / 1
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Forced expression of USP10 remarkably increases KLF4 protein level by blocking the latter degradation, whereas the depletion of USP10 promotes KLF4 degradation and thus enhances tumorigenesis.
USP10 increases the amount of KLF4.
| 1
Modified USP10 increases the amount of KLF4. 1 / 1
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Loss of USP10 in mice downregulates KLF4 expression and accelerates Kras G12D -driven lung adenocarcinoma initiation and progression.
USP10 affects His2Av
| 2
USP10 decreases the amount of His2Av.
| 1
USP10 decreases the amount of His2Av. 1 / 1
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Finally, knockdown of USP10 also impairs the loss of H2A.Z at the regulatory regions of PSA and KLK2 that normally occurs during their transcriptional activation.
USP10 activates His2Av.
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USP10 activates His2Av. 1 / 1
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In addition, knockdown of USP10 prevented full eviction of H2A.Z at the regulatory elements of AR regulated genes during their transcriptional activation.
USP10 affects ENaC
| 2
USP10 increases the amount of ENaC.
| 1
Modified USP10 increases the amount of ENaC. 1 / 1
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For instance, cell surface ENaC levels are increased by elevated expression of USP10, a condition that is physiologically mediated by vasopressin.
USP10 activates ENaC.
| 1
USP10 activates ENaC. 1 / 1
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Another DUB, USP10, is induced by vasopressin and enhances ENaC activity by deubiquitinating sorting nexin 3 instead of ENaC subunits directly [XREF_BIBR].
USP10 affects EIF4G1
| 2
USP10 inhibits EIF4G1.
| 1
USP10 inhibits EIF4G1. 1 / 1
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Using tandem affinity purification combined with mass spectrometry (TAP-MS) screening approach, we have identified that ubiquitin specific protease 10 (USP10) can directly interact with EIF4G1 and inhibit EIF4G1 activities in NSCLC cells [XREF_BIBR], although the underlying mechanism remains largely unknown and further investigations are warrant to solve this puzzle.
USP10 increases the amount of EIF4G1.
| 1
USP10 increases the amount of EIF4G1. 1 / 1
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There is a recent report that USP10 interacts with eIF4G1 and depletion of USP10 enhanced eIF4G1 protein levels.
USP10 affects BAX
| 2
USP10 increases the amount of BAX.
| 1
USP10 increases the amount of BAX. 1 / 1
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Reconstitution of USP10 in CAKI-1 and CAKI-2 (WT p53 cell lines) restored p53 expression and increased p21 and BAX expression (XREF_SUPPLEMENTARY).
USP10 decreases the amount of BAX.
| 1
USP10 decreases the amount of BAX. 1 / 1
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Interestingly, downregulation of USP10 significantly decreased p53 stabilization and the expression of p53 target genes p21 and Bax after DNA damage (XREF_FIG).
USP10 affects AS
| 1 1
USP10 inhibits AS.
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USP10 inhibits AS. 1 / 1
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Overexpressed USP10-WT inhibits AS-, TG-, or CZ-induced SGs ( xref , 1–3), but mutant USP10-F10A does not ( xref , 4–6).
USP10 activates AS.
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USP10 activates AS. 1 / 1
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In conclusion, USP10 promotes the development and progression of atherosclerosis through stabilizing CD36 protein expression.
USP10 affects AMPK_alpha
| 2
USP10 inhibits AMPK_alpha.
| 1
| 1

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USP10 was reported to inhibit tumor growth and inactivate mTORC1 and AKT signaling by stabilizing AMPKalpha and PTEN in HCC cells.
USP10 activates AMPK_alpha.
| 1
| 1

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In order to further clarify whether the USP10 mediated AMPKalpha activation is independent of LKB1, we transfected FLAG-AMPKalpha alone or in combination with MYC-USP10 in LKB1 deficient Hela cells.
USP10 affects AICDA
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USP10 increases the amount of AICDA.
| 1
USP10 increases the amount of AICDA. 1 / 1
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The deficiency of USP10 in B cells significantly decreased AID protein levels, subsequently reducing neutralizing antibody production after immunization with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or human immunodeficiency virus type 1 (HIV-1) nanoparticle vaccines.
USP10 activates AICDA.
| 1
USP10 activates AICDA. 1 / 1
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Collectively, we demonstrated that USP10 functions as an integrator for both BCR and TLR signals and directly regulates nuclear AID activity.

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Since the treatment of spautin-1 also led to reduced levels of USP10, which was inhibited by the addition of MG132 (XREF_SUPPLEMENTARY), it is likely that the levels of USP10 and USP13 are also regulated by ubiquitination.

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MG-132 treatment reduced the amount of USP10, and the reduction is attenuated by cotreatment with BafA1 (XREF_FIG B), indicating that USP10 is degraded by autophagy.
MYC affects USP10
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MYC increases the amount of USP10.
| 1
MYC increases the amount of USP10. 1 / 1
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USP10 also antagonizes c-myc transcription through deubiquitination of SIRT6, a histone deacetylase, and NF-kappaB signaling through deubiquitination of NEMO [XREF_BIBR].
MYC activates USP10.
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MYC activates USP10. 1 / 1
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Our studies indicate that USP10 induced by c-Myc has a crucial role in OIS by maintaining the stability of key tumor suppressor p14ARF.
His2Av affects USP10
| 2
His2Av inhibits USP10.
| 1
His2Av inhibits USP10. 1 / 1
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Since expression of H2A.Z is unaffected by knockdown of USP10 (see XREF_FIG C) this finding strongly suggests that USP10 is required for the transcription induced loss of H2A.Z at AR regulated genes.
His2Av activates USP10.
| 1
His2Av activates USP10. 1 / 1
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Finally, in vitro assays confirmed that H2A.Z is a direct target of USP10, as well as other DUBs such as USP16 and 2A-DUB.
Vorinostat affects USP10
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Vorinostat decreases the amount of USP10. 1 / 1
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No evidence text available
Vinclozolin affects USP10
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Vinclozolin decreases the amount of USP10. 1 / 1
1 |

ctd
No evidence text available
Topotecan affects USP10
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Topotecan decreases the amount of USP10. 1 / 1
1 |

ctd
No evidence text available
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Thioacetamide increases the amount of USP10. 1 / 1
1 |

ctd
No evidence text available
Thimerosal affects USP10
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Thimerosal decreases the amount of USP10. 1 / 1
1 |

ctd
No evidence text available
1 |
Sodium fluoride increases the amount of USP10. 1 / 1
1 |

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No evidence text available
1 |
Sodium arsenite increases the amount of USP10. 1 / 1
1 |

ctd
No evidence text available
1 |
Schizandrin B increases the amount of USP10. 1 / 1
1 |

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No evidence text available
Pyrogallol affects USP10
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Pyrogallol increases the amount of USP10. 1 / 1
1 |

ctd
No evidence text available
Potassium chromate increases the amount of USP10. 1 / 1
1 |

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No evidence text available
1 |

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No evidence text available
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Pentachlorophenol increases the amount of USP10. 1 / 1
1 |

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No evidence text available
Oxaliplatin affects USP10
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Oxaliplatin decreases the amount of USP10. 1 / 1
1 |

ctd
No evidence text available
Nimesulide affects USP10
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Nimesulide increases the amount of USP10. 1 / 1
1 |

ctd
No evidence text available
Nefazodone affects USP10
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Nefazodone increases the amount of USP10. 1 / 1
1 |

ctd
No evidence text available
Methyltestosterone decreases the amount of USP10. 1 / 1
1 |

ctd
No evidence text available
Ionomycin affects USP10
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Ionomycin increases the amount of USP10. 1 / 1
1 |

ctd
No evidence text available
1 |
Hsa-miR-98-5p decreases the amount of USP10. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-92a-3p decreases the amount of USP10. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-652-3p decreases the amount of USP10. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-455-3p decreases the amount of USP10. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
Hsa-miR-375 affects USP10
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Hsa-miR-375 decreases the amount of USP10. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-24-3p decreases the amount of USP10. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-20a-5p decreases the amount of USP10. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-181b-5p decreases the amount of USP10. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-124-3p decreases the amount of USP10. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
1 |
Hsa-miR-122-5p decreases the amount of USP10. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
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Hsa-let-7b-5p decreases the amount of USP10. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
Glucose affects USP10
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USP10 was found to be upregulated by glucose starvation and removed K63-linked polyubiquitin chains on alpha2-K60 and K391 , and analogous alpha1-K62 and K388 , to increase association with LKB1 .
1 |
Geldanamycin increases the amount of USP10. 1 / 1
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No evidence text available
Forkhead affects USP10
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Forkhead increases the amount of USP10. 1 / 1
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This study aimed to investigate whether forkhead box O4 (FoxO4) could negatively modulate ubiquitin specific peptidase 10 (USP10) transcription to aggravate the apoptosis and oxidative stress of hypoxia and reoxygenation (H/R)-induced cardiomyocytes through Hippo and YAP pathway.
Flutamide affects USP10
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Flutamide increases the amount of USP10. 1 / 1
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No evidence text available
Fenofibrate affects USP10
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Fenofibrate increases the amount of USP10. 1 / 1
1 |

ctd
No evidence text available
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Current studies are underway to elucidate the mechanism by which the epoxide hydrolase activity of Cif promotes the inactivation of USP10, via enhancement of G3BP1 interaction, leading to the degradation of CFTR.
1 |

ctd
No evidence text available
Endosulfan affects USP10
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Endosulfan increases the amount of USP10. 1 / 1
1 |

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No evidence text available
Doxycycline affects USP10
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XREF_FIG, doxycycline induction of USP10 shRNA (Dox+), but not the vehicle (Dox-), led to a significant reduction of USP10 in H23 cells.
Dicrotophos affects USP10
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Dicrotophos increases the amount of USP10. 1 / 1
1 |

ctd
No evidence text available
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Dexamethasone decreases the amount of USP10. 1 / 1
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Cobalt dichloride decreases the amount of USP10. 1 / 1
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No evidence text available
Barium(2+) affects USP10
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Our results showed that BA treatment (1) decreased USP10 activity in both LNCaP and 22Rv1; (2) decreased USP9X activity in 22Rv1; and (3) had little effect on USP7 activity.

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Another autophagy inhibitor, spautin-1, degrades class III PI3K by inhibiting the activity of the ubiquitin specific peptidases, USP10 and USP13 (Mateo et al., 2013, Liu et al., 2011).
Ato affects USP10
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Ato inhibits USP10. 1 / 1
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Previous reports had suggested that ATO could degrade FLT3 protein by downregulating USP10 to inhibit FLT3-ITD positive cells, but ATO at low concentrations (0.5 microM) failed to downregulate USP10 and could not induce degradation of total FLT3 and modulation of 160KD or 130KD FLT3 (Additional file 1 : Figure S1A, B).
AhpC affects USP10
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AhpC inhibits USP10. 1 / 1
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We found that mutation at either T42 or S337 partially affects USP10 stabilization and mutating both T42 and S337 (TS/AA) abolished USP10 stabilization following DNA damage (XREF_FIG and XREF_SUPPLEMENTARY).

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TIA-1 is not sequestered in DNA factories [143]; however, infection with a VV mutant lacking E3L, which activates PKR, induces aggregates that contain TIA-1, eIF3b, G3BP1 and USP10, called antiviral granules (AVGs), given that they restrict viral replication [94].
USP10 affects transport
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These results suggested that USP10 functions to stimulate transport of p62 aggregates to the perinuclear aggresome formation site.

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The cotransfection of USP10 could significantly upregulated T-bet mediated transcription activation, suggesting that USP10 may act as a positive regulator of T-bet.

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To further complicate matters , USP10 impairs SG assembly [ 32 ] , whereas p62 has been implicated in SG clearance [ 19 ] .
USP10 bound to G3BP2 inhibits signal transduction. 1 / 1
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For example, USP10 interacts with G3BP2 to block p53 signal transduction, leading to poor prognosis in prostate cancer [XREF_BIBR]; USP44 promotes the development of prostate cancer by stabilizing EZH2 [XREF_BIBR], and USP2a enhances c-Myc expression via microRNA related regulation and thus promotes tumourigenesis [XREF_BIBR].
USP10 affects secretion
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USP10 Promotes Fibronectin Recycling , Secretion , and Organization .

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In the case of DNA damage , the phosphorylation of USP10 at Thr42 and Ser337 mediated by ATM is essential for its translocation to the nucleus , where USP10 induces the deubiquitination of p53 and makes p53 work as a tumor suppressor ( Fig. 2c ) .122 In addition to ubiquitination , p53 can also undergo other ubiquitination-like modifications , such as neddylation and SUMOylation .
USP10 affects nppb
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USP10 decreases the amount of nppb. 1 / 1
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Compared with AdGFP transfection, AdUSP10 notably alleviated Ang II induced cardiomyocyte enlargement, accompanied by significant decreases in the expression of the fetal genes Anp, Bnp, and Myh7; in contrast, USP10 silencing significantly exacerbated myocyte hypertrophy and upregulated the expression of Anp, Bnp, and Myh7 compared with that in primary cells infected with AdshRNA, suggesting that USP10 can directly mitigate the hypertrophic growth of isolated myocytes induced by Ang II.

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USP10 exacerbates neointima formation by stabilizing Skp2 protein in vascular smooth muscle cells .
USP10 affects mTORC1
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USP10 inhibits mTORC1. 1 / 1
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USP10 was reported to inhibit tumor growth and inactivate mTORC1 and AKT signaling by stabilizing AMPKalpha and PTEN in HCC cells.
USP10 affects imidazolide
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To determine whether inhibition of USP10 enhances the efficacy of IM, we examined the effect of Spautin-1 or various concentrations of IM alone or in combination on the cell viability of CML cells and primary monocytes from patients.
USP10 affects hydrolase
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Furthermore, under energy stress, AMPK phosphorylates USP10 at Ser76 which increases its hydrolase activity.
USP10 affects helicase
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It is also possible that USP10 blocks the helicase function of G3BP, as helicase activity of some proteins, e.g., DDX6 and RCK, has been shown to be required for RNA granule assembly.
USP10 affects estrogen
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Usp10 overexpression abolished the estrogen mediated regulation of p53 and the downstream transcriptional gene p21.
USP10 affects elaD
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USP10 activates elaD. 1 / 1
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These results suggest that S76 phosphorylation of USP10 increases the deubiquitinase activity of USP10.
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USP10 overexpression blocks SG assembly (XREF_FIG), either by preventing polysome disassembly or by preventing mRNP condensation.
USP10 affects cisplatin
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Therefore, USP10 may decrease cisplatin sensitivity and serve an oncogenic role through HDAC6.

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Usp10 inhibition attenuated H 2 O 2 -induced senescence in MLO-Y4 cells, as indicated by p53 and p21 quantification, a senescence associated beta-galactosidase (SA-beta-gal) assay, and p53 localization visualization with a confocal microscope.
| 1

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The overexpression of Skp2 abrogated cell cycle arrest induced by USP10 inhibition.
USP10 affects amiloride
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Coexpression of Usp10 in ENaC transfected HEK-293 cells causes a more than fivefold increase in amiloride sensitive Na+ currents, as measured by whole cell patch clamping.
USP10 affects VIM
| 1
Modified USP10 decreases the amount of VIM. 1 / 1
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Reversely, overexpression of USP10 elevates the level of both Slug and Vimentin.
| 1

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USP10 decreases the ubiquitination of CFTR , whereas the knockdown of USP10 promotes the ubiquitination and reduction of CFTR at the cell surface [ 85 ] .
| PMC
USP10 affects USP22
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USP10 activates USP22. 1 / 1
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Usp10 is known to enhance AR transcriptional activity [XREF_BIBR, XREF_BIBR] and Usp22 and Usp26 have been found in complexes with AR [XREF_BIBR, XREF_BIBR].
USP10 affects SLC9A3
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USP10 decreases the amount of SLC9A3. 1 / 1
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Knockdown of USP7 or USP10 resulted in increased NHE3 ubiquitination and decreased NHE3 expression at the surface membrane and cellular level.
USP10 affects SEC23
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USP10 activates SEC23. 1 / 1
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The interaction of G3BP with USP-10 rescues Sec23 and beta-COP transcripts from degradation, maintaining the activity of anterograde and retrograde protein secretion pathways.
USP10 affects S4
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USP10 activates S4. 1 / 1
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XREF_FIG and S4), suggesting that p53 is a determinant for growth in vivo mediated by USP10.
USP10 affects Recycling
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Endosome-localized DUB , Ubiquitin Specific Protease 10 ( USP10 ) , suppresses ubiquitylation of WT-CFTR in early endosomes and promotes the recycling of CFTR to the PM [ 55 ] .
USP10 affects RPS6
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USP10 decreases the amount of RPS6. 1 / 1
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As anticipated, overexpressing USP10 markedly inhibited the expression of P-AKT and P-S6, and increases P-AMPKalpha expression in vivo.
USP10 affects RAF1
| 1
Modified USP10 increases the amount of RAF1. 1 / 1
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USP10 overexpression promoted Raf-1 protein expression, but not the mRNA expression, through deubiquitination.
USP10 affects PSMA7
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USP10 inhibits PSMA7. 1 / 1
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These results suggest that SCF signaling and its associated factors function in USP10 mediated inhibition of HSPC apoptosis.
USP10 affects PI3K
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USP10 inhibits PI3K. 1 / 1
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While A20 inhibits PtdIns3P signaling by removing the TRAF6 dependent Lys63 linked chains from Beclin 1, the enzymes USP10 and USP13 prevent PI3K and III complex components from their degradation and, therefore, support autophagy.
USP10 affects NOTCH1
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USP10 activates NOTCH1. 1 / 1
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In conclusion, our results revealed a novel mechanism by which USP10-mediated activation of Notch1 plays a protective role against MI injury in T2DM mice.
| PMC
USP10 affects NFE2L2
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USP10 activates NFE2L2. 1 / 1
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This study found that USP10 activates the NRF2 and ARE signaling through SIRT6.
| 1

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Accordingly , inactivation of USP10 reduced Sirt6 abundance and stability and diminished Sirt6-induced downstream signaling in cardiomyocytes .
USP10 affects MYH7
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Modified USP10 decreases the amount of MYH7. 1 / 1
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Furthermore, overexpression of wild-type USP10 inhibits cardiomyocyte enlargement and the expression of ANP, BNP, and Myh7, whereas overexpression of mutant USP10 eliminated this effect.
USP10 affects MPZ
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USP10 inhibits MPZ. 1 / 1
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These results suggest that inhibition of HSC apoptosis is a function of USP10 to maintain the number of HSCs in FL, and that USP10 selectively inhibits apoptosis of HSCs, MPPs, and HPCs but not more differentiated LCPs.
USP10 affects MITF
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USP10 activates MITF. 1 / 1
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However, the pathological role of Notch1/USP10 signaling in MI-induced cardiac remodeling and fibrosis in T2DM remains largely unexplored.
| PMC
USP10 affects MEK
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USP10 activates MEK. 1 / 1
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USP10 overexpression promoted ectopic endometrial stromal cell migration and proliferation, suppressed cell apoptosis, and activated MEK and ERK signaling that is a critical downstream target of the serine/threonine protein kinase Raf-1, which was significantly blocked by PD98059.
USP10 affects Integrins
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USP10 overexpression increased α5β1 (1.9-fold; P < 0.001) and αv (1.7-fold; P < 0.05) integrin recycling, with a concomitant increase in biotinylated FN internalization (2.1-fold; P < 0.05) and recycling over 4 days (1.7-2.2-fold; P < 0.05).
USP10 affects IFNG
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USP10 activates IFNG. 1 / 1
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Although the underlying mechanism of T-bet ubiquitination is unknown, USP10 has been found to stabilize T-bet via deubiquitination and enhance the secretion of IFN-gamma.
USP10 affects HUWE1
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USP10 inhibits HUWE1. 1 / 1
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We found that Huwe1 activity on TBP is antagonized by the deubiquitinase USP10, which protects TBP from degradation.
USP10 affects FN1
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USP10 activates FN1. 1 / 1
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USP10 Promotes Fibronectin Recycling, Secretion, and Organization.
USP10 affects ERK
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USP10 activates ERK. 1 / 1
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USP10 overexpression promoted ectopic endometrial stromal cell migration and proliferation, suppressed cell apoptosis, and activated MEK and ERK signaling that is a critical downstream target of the serine/threonine protein kinase Raf-1, which was significantly blocked by PD98059.
USP10 affects EDNRA
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USP10 activates EDNRA. 1 / 1
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USP10 activity on PCNA promotes the release of Pol eta and terminates TLS [XREF_BIBR].
USP10 affects Death
| 1
USP10 inhibits Death. 1 / 1
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USP10 inhibition leads to death of cells driven by active SYK or oncogenic FLT3 and potentiates the anti-leukemic effects of FLT3 inhibition in these cells.

reach
Meanwhile, Increased expression of USP10 in prostate cancer cells in interaction with G3BP2 inhibits the P53 signaling pathway and causes a specific carcinogenic effect along the USP10 / G3BP2 / P53 pathway (Takayama et al., 2018).
| PMC
USP10 affects CDKN2A
| 1
USP10 activates CDKN2A. 1 / 1
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USP10 loss, p14ARF loss, and dual loss of USP10 and p14ARF were significantly associated with shorter disease-free survival and overall survival in comparison to USP10 intact, p14ARF intact, and dual loss of USP10 and p14ARF, respectively.
USP10 affects CASP3
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USP10 inhibits CASP3. 1 / 1
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Thus, we examined whether USP10 inhibits MG-132-induced cell death by measuring activated caspase-3 (cleaved caspase-3).
USP10 affects CAPRIN1
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USP10 activates CAPRIN1. 1 / 1
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G3BP-binding and SG-inhibiting variants of USP10 and SFV-nsP3 (XREF_FIG, lanes 3, 5, 6, and 8) selectively decrease G3BP1/2 and Caprin1 B-isox precipitation without affecting that of TIA-1, TIAR, TDP43, or PABP.
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USP10 alleviates Ang II ( angiotensin II ) - induced cardiomyocyte hypertrophy in vitro .
U3 affects USP10
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U3 inhibits USP10. 1 / 1
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The effect of USP10 down-regulation by si-U1 and si-U3 on androgen stimulated MMTV activity was then determined.
U1 affects USP10
| 1
U1 inhibits USP10. 1 / 1
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The effect of USP10 down-regulation by si-U1 and si-U3 on androgen stimulated MMTV activity was then determined.
Tax affects USP10
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Tax inhibits USP10. 1 / 1
| 1

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The Human T-Lymphotropic Virus 1 (HTLV1) Tax protein blocks SG assembly by interacting with the SG components histone deacetylase 6 (HDAC6) (Legros et al., 2011) and USP10 (Takahashi et al., 2013).
TBP affects USP10
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TBP activates USP10. 1 / 1
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Importantly, both western blot and flow cytometry analysis confirmed modestly increased TBP protein levels in a C2C12 stable cell line overexpressing USP10 (XREF_FIG, XREF_FIG).
Sesame Oil affects USP10
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Sesame Oil increases the amount of USP10. 1 / 1
1 |

ctd
No evidence text available

reach
To confirm that translocated USP10 is functional, we fractionated cells treated with IR.
Niclosamide affects USP10
1 |
Niclosamide decreases the amount of USP10. 1 / 1
1 |

ctd
No evidence text available
NLRP7 affects USP10
| 1
NLRP7 inhibits USP10. 1 / 1
| 1

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Downregulation of USP10 expression significantly suppressed the proliferative, migration, and invasive capabilities of HCT116 and SW480 cells, whereas overexpression of NLRP7 attenuated the inhibitory effect of USP10 silencing.
MTOR affects USP10
| 1
MTOR activates USP10. 1 / 1
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Therefore, we conclude that USP10 interacts with PTEN and AMPKalpha, inhibits their polyubiquitylation, and as a result stabilizes PTEN and AMPKalpha.Next, we examined whether Rapamycin, a well known [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
MITF affects USP10
| 1
MITF activates USP10. 1 / 1
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In conclusion, FSTL1 treatment ameliorated cardiac dysfunction in MI with co-existent T2DM, possibly through inhibition of myocardial fibrosis and apoptosis by upregulating USP10/Notch1 signaling.
| PMC
MAP3K7 affects USP10
| 1
MAP3K7 activates USP10. 1 / 1
| 1

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TAK1 was required for USP10 function in hepatic I/R injury as TAK1 inhibition abolished USP10 function in vitro.
KITLG affects USP10
| 1
KITLG inhibits USP10. 1 / 1
| 1

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These results suggest that the amount of SCF secreted in the FL niche is sufficient to inhibit apoptosis of USP10-WT but not USP10-KO HSPCs, thereby reducing the number of HSPCs in USP10-KO FL.
IL1B affects USP10
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IL1B activates USP10. 1 / 1
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In addition to genotoxic stress, the TANK, MCPIP1, and USP10 complex is also responsible for restraining TRAF6 ubiquitination in cells treated with LPS or IL-1beta.
HDAC_III affects USP10
| 1
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USP10 physically binds to sirtuin 6 and sirtuin 6 mediates the effect of USP10 on the regulation of cardiac hypertrophy.
GASAL1 affects USP10
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GASAL1 activates USP10. 1 / 1
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GASAL1 could up-regulate USP10 via competitively binding to miR-193b-5p .
EIF4G affects USP10
| 1
EIF4G inhibits USP10. 1 / 1
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Our previous study showed that EIF4G1 combined with USP10 in the lung cancer cell line A549, as determined by co-immunoprecipitation analysis, so we assume that EIF4G1 can inhibit the USP10 mediated stabilization of p53 by binding to USP10, leading to the inhibition of p53 functions in cancer cells.
| 1
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On the other hand, the Japanese encephalitis virus (JEV) core protein was shown to sequester G3BP1 and USP10 through an interaction with Caprin1, resulting in the suppression of SG formation [174].
CPG-oligonucleotide decreases the amount of USP10. 1 / 1
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CAPRIN1 affects USP10
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This shows that Caprin1 prevents G3BP1 from binding to immobilized USP10 8-25 WT in a dose dependent manner, confirming that G3BP1-USP10 and G3BP1-Caprin1 complexes result from direct protein protein binding and that competition between Caprin1 and USP10 for G3BP1 occurs in solution as well as in cells.
CALML3 affects USP10
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CALML3 activates USP10. 1 / 1
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We identified that USP10 alleviated renal dysfunction induced by CLP.
BRE5 affects USP10
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BRE5 inhibits USP10. 1 / 1
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Surprisingly, the human homolog of Bre5, G3BP1, inhibits the activity of USP10, at least in vitro, indicating that cofactors can either restrict or enhance protease activity.
ATM affects USP10
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ATM activates USP10. 1 / 1
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ROS-induced stress promotes ATM-dependent USP10 activation.
AR affects USP10
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AR increases the amount of USP10. 1 / 1
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USP10 and H2A.Z regulate AR mediated transcription.
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4,4'-sulfonyldiphenol decreases the amount of USP10. 1 / 1
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No evidence text available