IndraLab
Statements
reach
"6 In OSCC tissues, PTEN expression is downregulated and negatively associated with activated AKT.7 10 Consistent with earlier findings, USP13 increased PTEN protein levels and decreased p-AKT levels in OSCC cells, and overexpression of PTEN partially reversed the USP13-knockdown-induced glucose uptake and lactate production in the present study.Loss of PTEN and abnormal AKT activation influences the regulation of various downstream effectors, thus contributing to tumorigenesis.11 13 GLUT1 and HK2 are important glycolysis regulators downstream of the AKT pathway.26 27 AKT activity is essential for insulin-induced GLUT1 gene expression."
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"Collectively, these data suggest that loss of USP13 may contribute to loss of PTEN in a substantial fraction of human tumors, whereas in other tumors PTEN can be inactivated by different mechanisms, including genetic alterations and upregulation of PTEN ubiquitin ligases (such as NEDD4-1 14 and WWP2 15)."
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"For example, overexpression of USP13 blocks the AKT signaling pathway and suppresses tumor cell proliferation, invasion, and glycolysis by upregulating PTEN, while USP13 levels are downregulated in breast, bladder, and oral squamous tumors, in correlation with PTEN levels (Fig. 3)."
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"The coding sequence of USP13 or PTEN was amplified with the following primers: USP13 (NM_003940.2), forward 5′-CGGAATTCATGCAGCGCCGGG-3′ and reverse 5′-CGGGATCCTTAGCTTGGTATCCTGCGG-3′; and PTEN (CR450306.1), forward 5′-CGGAATTCATGACAGCCATCATCAAAGAG-3′ and reverse 5′-CGGGATCCCGATCTCTTTGATGATGGCTG-3′."
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"Two independent USP13 shRNAs both decreased PTEN protein expression by 80% and increased phospho-AKT and phospho-FOXO1/3 levels by 3- to 5-fold in SUM159 breast cancer cells, while restoration of PTEN or expression of an RNAi resistant ' silence mutant ' (i.e., no amino acid change) of USP13 (USP13-RE) in USP13 depleted SUM159 cells completely reversed the effect of USP13 shRNA on upregulating the phosphorylation of AKT and FOXO (XREF_FIG and XREF_SUPPLEMENTARY)."
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"Following DNA damage, phosphorylated USP13 by ATM is recruited to DNA damage sites to cleave the ubiquitin chains from more than three sites of RAP80 (K75, K90, and K112), releasing their restriction on the K63-linked ubiquitin chain, improving the focus formation of the RAP80-BRCA1 complex, and eventually facilitating DDR."
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"We demonstrated that (1) a recurrent Q607R somatic substitution in CLK3 was identified in 8% of 100 human CCAs, particularly in patients with CCA metastasis; (2) the expression of CLK3 was significantly up-regulated in CCA compared with matched control tissues; (3) CLK3 knockdown significantly inhibited CCA aggressiveness in vitro and in vivo; (4) gene ontology term enrichment and MS assays indicated that high CLK3 expression in CCA patients mainly regulated nucleotide metabolism, especially purine biosynthesis; (5) mechanistically, CLK3 directly phosphorylated USP13 at Y708, which promoted its binding to c-Myc, a critical purine synthesis–associated transcription factor, thereby preventing Fbxl14-mediated c-Myc ubiquitination and activating the transcription of purine metabolic genes; (6) the CCA-associated CLK3-Q607R mutant induced USP13-Y708 phosphorylation and enhanced the activity of c-Myc; (7) in turn, c-Myc transcriptionally up-regulated CLK3; (8) importantly, levels of CLK3 significantly correlated with the expression of phospho-USP13-Y708, c-Myc, and ATIC in human CCA specimens; and (9) tacrine hydrochloride was identified as a potential compound to inhibit the aberrant CLK3-enhanced CCA invasiveness."
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"Aurora B and ataxia telangiectasia mutated (ATM) regulate the expression of USP13 via phosphorylation of USP13 at Ser114 and Thr196 to promote the interaction between them, respectively, while the CDC-like kinase 3 (CLK3)-Q607R mutation induces the phosphorylation of USP13 at Tyr708 and promotes its association with c-Myc ( xref )."
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"In cholangiocarcinoma, TGF-β signaling triggers the phosphorylation of CLK3, a serine/threonine kinase that directly phosphorylates USP13 at Y708 and facilitates USP13 interaction with c-Myc ( xref ); in GSCs, USP13 can enhance the stability through deubiquitinating c-Myc, activating purine synthesis mediated by c-Myc and inducing the tumorigenesis of GSCs ( xref ); in hepatocellular carcinoma, knockdown of USP13 by shRNA can markedly downregulate c-Myc expression, resisting xenograft tumor growth of HCC ( xref )."
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"Aurora B and ataxia telangiectasia mutated (ATM) regulate the expression of USP13 via phosphorylation of USP13 at Ser114 and Thr196 to promote the interaction between them, respectively, while the CDC-like kinase 3 (CLK3)-Q607R mutation induces the phosphorylation of USP13 at Tyr708 and promotes its association with c-Myc ( xref )."
rlimsp
"As shown in Supplementary Fig. 8c, T196 was phosphorylated after DNA damage, and the T196A mutation inhibited USP13 phosphorylation after DNA damage. In addition, USP13 was phosphorylated on Thr196 following DNA damage in ATM-proficient cells but not ATM-deficient cells (Fig. 5c), suggesting ATM phosphorylates USP13 on T196 following DNA damage."
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"Specifically, Esposito et al. found that Aurora kinase B, crucial for mitosis, phosphorylates USP13 at the serine 114 and that this phosphorylation enhances the interaction of both proteins, thereby maintaining the stability of Aurora kinase B. Intriguingly, USP13 stabilizes Aurora kinase B by modulating its ubiquitination, a process that occurs independently of its DUB activity."
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"Aurora B and ataxia telangiectasia mutated (ATM) regulate the expression of USP13 via phosphorylation of USP13 at Ser114 and Thr196 to promote the interaction between them, respectively, while the CDC-like kinase 3 (CLK3)-Q607R mutation induces the phosphorylation of USP13 at Tyr708 and promotes its association with c-Myc ( xref )."
USP13 is phosphorylated on T196. 2 / 2
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"(e) Control, USP13 knockout, and USP13 knockout cells stably expressing the indicated constructs were subjected to colony formation assay to assess the sensitivity of cells to cisplatin. Error bars represent±s.e.m. from three independent experiments. (f) HEK293T cells transfected with HA-MDC1 were left untreated or treated with cisplatin. Cell lysates were subjected to immunoprecipitation with HA antibody. The immunoprecipitates were then blotted with the indicated antibodies. (g) HEK293T cells transfected with deletion mutants of HA-MDC1 were subjected to co-immunoprecipitation as in f. (h) HEK293T cells transfected with WT or T196A USP13 were treated with cisplatin, and cell lysates were incubated with Sepharose coupled with GST or GST-MDC1-FHA domain. After washing, proteins bound on Sepharose were blotted with the indicated antibodies. (i) Nonphosphorylated or phosphorylated Thr 196 peptide (T196 or p-T196, respectively) was conjugated to Sepharose beads and incubated with purified GST-MDC1-FHA domain in NETN buffer."
USP13 is ubiquitinated.
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"NEDD4 undergoes K29-linked auto-ubiquitination at K1279 and serves as a scaffold for recruiting USP13 to form a NEDD4-USP13 deubiquitination complex, which subsequently cleaves the K48-linked poly-ubiquitin chains from PIK3C3 at K419, thus stabilizing PIK3C3 to promote autophagy.
the ubiquitination of USP13; however, NEDD4 appears to be its own substrate for ubiquitination, and the catalytic activity of NEDD4 is required for its auto-ubiquitination."
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"Protein interaction experiments demonstrated that USP13 could co-immunoprecipitate with endogenous TopBP1, and in vitro deubiquitination enzyme experiments showed that WT-USP13 could deubiquitinate TopBP1, while CA-USP13 could not, highlighting the requirement for USP13 ubiquitination activity ( xref )."
"Collectively, we nominate <span class="match term0">USP13</span> as a novel deubiquitinase which regulates <span class="match term1">MCL1</span> turnover in diverse solid tumors and propose that <span class="match term0">USP13</span> may be a potential therapeutic target for the treatment of various malignancies."
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"We confirmed the siRNA screen results by transfecting each of the four oligos against USP13 into HEK293T cells, and indeed found that USP13 knockdown decreased the endogenous protein levels of MCL1, while modulating USP9X or OTUB2 with different siRNAs had no consistent effects on MCL1 expression."
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"Interestingly, Zhang et al. showed that pharmacological inhibition of USP13 by a small-molecule inhibitor, spautin-1, markedly downregulated MCL1 protein levels and sensitized ovarian and lung cancer cells to ABT-263, a selective antagonist of BCL-2 and BCL-XL.We selected DUB3 as an ideal target in ovarian cancer due to its oncogenic functions in various cancer subtypes ."
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"In addition, genetic depletion of USP13 using clustered regularly interspaced palindromic repeats (CRISPR)/Cas9, or pharmacological inhibition of USP13 by a small-molecule inhibitor spautin-1, markedly downregulates MCL1 protein expression and shows synergistic effects against tumor cells in combination with ABT-263, a selective antagonist of BCL-2 and BCL-XL."
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"Hence, pharmaceutical intervention of USP13 activity is expected to antagonize the tumorigenic potential of MCL1 oncoprotein, and combined administration of USP13 inhibitors with clinically approved venetoclax therapy may represent a promising targeting strategy for the treatment of human cancer by inducing tumor cell death."
USP13 affects cell population proliferation
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USP13 activates cell population proliferation.
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"Ectopically expressed K488R of METTL3 significantly promoted cell proliferation and glycolysis, while USP13 knockdown decreased cell proliferation and glycolysis with WT METTL3 rather than K488R METTL3, which indicated that mutation of K488 of METTL3 promoted cell proliferation and glycolysis and abolished USP13 depletion-induced proliferation and glycolysis suppression (Fig. 4i-n)."
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"USP13 has been shown to upregulate fatty acid synthase (FASN) to promote the proliferation of SCLC cells and Twist-related protein 1 (Twist1) to promote the migration and invasion of breast cancer cells, while it inhibits cell proliferation via downregulation of glycolysis in oral squamous cell carcinoma (47,48)."
USP13 inhibits cell population proliferation.
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"For example, overexpression of USP13 blocks the AKT signaling pathway and suppresses tumor cell proliferation, invasion, and glycolysis by upregulating PTEN, while USP13 levels are downregulated in breast, bladder, and oral squamous tumors, in correlation with PTEN levels (Fig. 3)."
Modified USP13 inhibits cell population proliferation. 2 / 2
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"Collectively, these data demonstrate that the ubiquitination insensitive mutant of c-Myc is able to rescue the phenotypes caused by USP13 knockdown or FBXL14 overexpression in vitro and in vivo, which supports that USP13 and FBXL14 mediate posttranslational regulation of c-Myc to control the stem cell like phenotype and tumorigenic potential of GSCs."
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"Aurora B and ataxia telangiectasia mutated (ATM) regulate the expression of USP13 via phosphorylation of USP13 at Ser114 and Thr196 to promote the interaction between them, respectively, while the CDC-like kinase 3 (CLK3)-Q607R mutation induces the phosphorylation of USP13 at Tyr708 and promotes its association with c-Myc (43)."
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"In cholangiocarcinoma, TGF-β signaling triggers the phosphorylation of CLK3, a serine/threonine kinase that directly phosphorylates USP13 at Y708 and facilitates USP13 interaction with c-Myc (Zhou et al., 2020); in GSCs, USP13 can enhance the stability through deubiquitinating c-Myc, activating purine synthesis mediated by c-Myc and inducing the tumorigenesis of GSCs (Fang et al., 2017); in hepatocellular carcinoma, knockdown of USP13 by shRNA can markedly downregulate c-Myc expression, resisting xenograft tumor growth of HCC (Huang et al., 2020)."
"In this study, we demonstrate that the deubiquitinase <span class="match term0">USP13</span> stabilizes c-<span class="match term1">Myc</span> by antagonizing FBXL14-mediated ubiquitination to maintain GSC self-renewal and tumorigenic potential."
"In this study, we demonstrate that the deubiquitinase USP13 stabilizes c-Myc by antagonizing FBXL14-mediated ubiquitination to maintain GSC self-renewal and tumorigenic potential. USP13 was preferentially expressed in GSCs, and its depletion potently inhibited GSC proliferation and tumor growth by promoting c-Myc ubiquitination and degradation."
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"As USP13 functions as a deubiquitinase that also interacts with c-Myc (XREF_FIG) and the preferential expression of USP13 in GSCs positively regulates c-Myc protein levels (XREF_FIG), we hypothesized that USP13 might mediate deubiquitination of c-Myc protein to prevent its degradation and stabilize c-Myc in GSCs."
"In this study, we demonstrate that the deubiquitinase USP13 stabilizes c-Myc by antagonizing FBXL14-mediated ubiquitination to maintain GSC self-renewal and tumorigenic potential. USP13 was preferentially expressed in GSCs, and its depletion potently inhibited GSC proliferation and tumor growth by promoting c-Myc ubiquitination and degradation."
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"In cholangiocarcinoma, TGF-β signaling triggers the phosphorylation of CLK3, a serine/threonine kinase that directly phosphorylates USP13 at Y708 and facilitates USP13 interaction with c-Myc (Zhou et al., 2020); in GSCs, USP13 can enhance the stability through deubiquitinating c-Myc, activating purine synthesis mediated by c-Myc and inducing the tumorigenesis of GSCs (Fang et al., 2017); in hepatocellular carcinoma, knockdown of USP13 by shRNA can markedly downregulate c-Myc expression, resisting xenograft tumor growth of HCC (Huang et al., 2020)."
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"20 In addition, USP13 is aberrantly overexpressed in ovarian cancers, and USP13 drives ovarian cancer metabolism by deubiquitinating ATP citrate lyase and oxoglutarate dehydrogenase.21 USP13 disruption inhibited the proliferation of glioma stem cells by promoting the ubiquitination and degradation of c-Myc."
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"Moreover, treatment with a proteasome inhibitor blocked the c-Myc loss caused by USP13 knockdown (not depicted), but overexpression of USP13 delayed c-Myc turnover in the presence of cycloheximide (not depicted), suggesting a critical role of USP13 in preventing proteasomal degradation of c-Myc in GSCs."
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"In 2011, Yuan et al. found that USP13 could interact with the C-terminal domain of Beclin-1 subunit in the VPS34 complex and deubiquitinate Beclin-1, thereby enhancing the stability of the VPS34 complex, which would contribute to the formation of autophagosomes (Liu et al., 2011)."
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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]."
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"To further verify the involvement of K29- and K48-linked polyubiquitination of WWP1 by USP13, we co-transfected Myc-WWP1 with wild-type (WT) HA-Ub or HA-Ub with a single lysine mutation (K6R, K11R, K27R, K29R, K33R, K48R, or K63R), along with or without Flag-USP13, into HEK293T cells (Fig. xref I)."
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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]."
"We found that endogenous Beclin1 can interact with USP13 and the interaction was reduced in the presence of spautin-1 (Figure 5C). Interestingly, the DUB activities were significantly increased when USP13 and USP10 coincubated together or with Beclin1 or all 3 proteins together, suggesting the DUB activity can be significantly enhanced when USP13 interacts with its substrate Beclin1 or USP10."
"We found that endogenous Beclin1 can interact with USP13 and the interaction was reduced in the presence of spautin-1 (Figure 5C). Interestingly, the DUB activities were significantly increased when USP13 and USP10 coincubated together or with Beclin1 or all 3 proteins together, suggesting the DUB activity can be significantly enhanced when USP13 interacts with its substrate Beclin1 or USP10."
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"In contrast, the truncate (aa301-863) that preserves DUB activity and UBA motifs inhibited cGAS and STING-mediated activation of IFN-β promoter and catalysed deubiquitination of STING ( xref ), indicating that USP13-mediated deubiquitination of STING is associated with its suppression of antiviral signalling."
Spautin-1 affects USP13
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Spautin-1 inhibits USP13.
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"A study by Liu et al. (Liu et al., 2011) has demonstrated that Spautin-1 is a potent small-molecule inhibitor of USP10 and USP13, and treatment with Spautin-1 inhibits the deubiquitinase activity of USP10 and USP13, resulting in an increasing ubiquitination and accelerating degradation of Beclin1 in Vps34 complexes, ultimately inhibiting autophagy."
Spautin-1 activates USP13.
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Spautin-1 ubiquitinates USP13.
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Lipopolysaccharide affects USP13
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Lipopolysaccharide inhibits USP13.
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Lipopolysaccharide decreases the amount of USP13.
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Lipopolysaccharide ubiquitinates USP13.
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Lipopolysaccharide leads to the ubiquitination of USP13. 2 / 2
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Lipopolysaccharide activates USP13.
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Lipopolysaccharide activates USP13. 2 / 2
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"In this study, we investigated the effect of isopeptidase T-3, also called USP13, on HMGB1, since HMGB1 ubiquitination has rarely been reported.To confirm whether USP13 binds to HMGB1, both Myc-HMGB1 and Flag-tagged USP13 (Flag-USP13) or USP10 and USP15 plasmids were overexpressed in HEK293T cells for co-immunoprecipitation."
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"Although our research results indicate that Spautin-1 exerts anti-tumor activity dependent on the induction of PANoptosis, there are still three key limitations that need to be addressed: (1) The mechanism by which Spautin-1 regulates the USP13-ACLY axis has not been thoroughly verified. (2) The expression pattern and prognostic value of USP13 have not yet been verified in clinical samples."
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"In ovarian tumors, upregulation of USP13 enhances deubiquitination and stabilization of ACLY (ATP citrate lyase) and OGDH (oxoglutarate dehydrogenase), two key enzymes that drive glutaminolysis, ATP generation, and lipid synthesis in cancer metabolism , and MCL1, a pivotal member of the antiapoptotic BCL-2 family of proteins ."
"<span class="match term0">USP13</span>, the main regulator of ovarian cancer energy metabolism, specifically deubiquitinates and stabilizes oxoglutarate dehydrogenase and ATP citrate lyase, which can catalyze fatty acid synthesis, glutaminolysis and mitochondrial respiration."
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"Taken together, these studies suggest that USP14 is involved in the occurrence and progression of multiple malignant tumors.Other USP family members: USP13, the main regulator of ovarian cancer energy metabolism, specifically deubiquitinates and stabilizes oxoglutarate dehydrogenase and ATP citrate lyase, which can catalyze fatty acid synthesis, glutaminolysis and mitochondrial respiration."
sparser
"NEDD4 undergoes K29-linked auto-ubiquitination at K1279 and serves as a scaffold for recruiting USP13 to form a NEDD4-USP13 deubiquitination complex, which subsequently cleaves the K48-linked poly-ubiquitin chains from PIK3C3 at K419, thus stabilizing PIK3C3 to promote autophagy.
the ubiquitination of USP13; however, NEDD4 appears to be its own substrate for ubiquitination, and the catalytic activity of NEDD4 is required for its auto-ubiquitination."
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"To further confirm the interaction between USP13 and cohesin, endogenous cohesin was immunoprecipitated with SMC3 antibodies from whole cell lysates prepared from genetically unmodified HCT116 cells and Western blot performed with USP13 antibodies (and STAG2 antibodies as a positive control)."
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"Although the biochemical and molecular functions of USP13 have been explored in various human cancers, including breast cancer, the oncogenic or tumor suppressor roles of USP13 in different studies has remained controversial.Here, we investigated a potential physical/functional interaction between Twist1 and USP13 in human breast cancer."
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"Moreover, USP13 had no effect on the ubiquitination of Twist1 by β-Trcp1, presumably due to the ineffectiveness of USP13 in Twist1 phosphorylation.As a typical transcription factor, Twist1 can recognize and bind to the E-box region of downstream gene promoters to activate or inhibit the transcription of target genes [68]."
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"A possible, but one-sided explanation may be that normal physiological concentrations of Twist1 individually inhibit USP13 promoter activation, whereas abnormal expression of USP13 may induce Twist1 to recruit co-factors to promote the transcription of its target genes including USP13."
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"USP13 has been shown to upregulate fatty acid synthase (FASN) to promote the proliferation of SCLC cells and Twist-related protein 1 (Twist1) to promote the migration and invasion of breast cancer cells, while it inhibits cell proliferation via downregulation of glycolysis in oral squamous cell carcinoma (47,48)."
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"Interestingly, NEDD4-1 undergoes auto-ubiquitination that serves it as a scaffold for engaging the ubiquitin-specific protease 13 (USP13) to form a NEDD4-1/USP13 deubiquitination complex, which subsequently deubiquitinates and stabilizes VPS34 to induce phagophore nucleation in cancer cells."
"Auto-ubiquitination of NEDD4-1 Recruits <span class="match term0">USP13</span> to Facilitate Autophagy through Deubiquitinating <span class="match term1">VPS34</span>"
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"Since USP13 could regulate several substrates in other cancers including MCL1, SKP2, MITF, PTEN, TOPBP1, and c-MYC as described above, ZHX2 could be one of downstream targets for USP13 and other substrates could contribute to the lack of complete rescue in ccRCC, which remains to be further explored.Spautin-1 was previously found to be the inhibitor for both USP10 and USP13 by promoting the degradation of Vps34 (39)."
USP13 affects Neoplasm Metastasis
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USP13 activates Neoplasm Metastasis.
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USP13 inhibits Neoplasm Metastasis.
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"In pulmonary metastatic models, a reduction in pulmonary metastasis caused by USP13 knockdown was abolished in 143B cells with METTL3 overexpression, while silencing METTL3 in HOS cells markedly counteracted the pro-metastatic influence of USP13 upregulation on pulmonary metastasis, as evidenced by histological analysis (Fig. 5f, g)."
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"In contrast, the truncate (aa301-863) that preserves DUB activity and UBA motifs inhibited cGAS and STING-mediated activation of IFN-β promoter and catalysed deubiquitination of STING ( xref ), indicating that USP13-mediated deubiquitination of STING is associated with its suppression of antiviral signalling."
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"Our results showed that USP13 short hairpin RNA inhibited ZHX2 expression and ccRCC cell growth, while these changes were rescued by the USP13 cDNA (short hairpin RNAs resistant) (SI Appendix, Fig. S4C and Fig. 3 D–G), revealing that the effect of USP13 short hairpin RNA on ZHX2 and soft agar growth was on-target."
USP13 affects Neoplasm Invasiveness
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USP13 activates Neoplasm Invasiveness.
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USP13 inhibits Neoplasm Invasiveness.
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"For example, overexpression of USP13 blocks the AKT signaling pathway and suppresses tumor cell proliferation, invasion, and glycolysis by upregulating PTEN, while USP13 levels are downregulated in breast, bladder, and oral squamous tumors, in correlation with PTEN levels (Fig. 3)."
sparser
"To further confirm the interaction between USP13 and cohesin, endogenous cohesin was immunoprecipitated with SMC3 antibodies from whole cell lysates prepared from genetically unmodified HCT116 cells and Western blot performed with USP13 antibodies (and STAG2 antibodies as a positive control)."
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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."
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"ROR1, after binding to Wnt ligands, triggers non-canonical signaling cascades that increase the level of calcium or decrease the level of cGMP within the cell, and these changes are closely associated with COPD onset and progression.51 SEC14L4 is known to be differentially expressed in COPD.52 USP13, which inhibits autophagy, may be involved in COPD pathogenesis.53,54Among the 11 feature genes, RS1 has not previously been linked to COPD, and our study justifies further exploration of this potential link."
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"Ectopically expressed K488R of METTL3 significantly promoted cell proliferation and glycolysis, while USP13 knockdown decreased cell proliferation and glycolysis with WT METTL3 rather than K488R METTL3, which indicated that mutation of K488 of METTL3 promoted cell proliferation and glycolysis and abolished USP13 depletion-induced proliferation and glycolysis suppression (Fig. 4i-n)."
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"Interestingly, USP13 associates with gp78 to attenuate polyubiquitination of ubiquitin-like protein 4A (UBL4A), a part of the Bag6 complex that helps chaperone retrotranslocated ERAD substrates to the proteasome, thereby protecting the Bag6 complex from proteasomal degradation and maintaining an adequate ERAD pathway, highlighting the importance of the associated DUB activity during ERAD [ xref ]."
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"Because the accumulation of Bag6 * upon USP13 depletion is significantly reduced in cells co-depleted of USP13 and gp78 (XREF_FIG), we propose that USP13 is required to antagonize a promiscuous activity of gp78 towards Ubl4A, which would otherwise impair the function of the Bag6 complex by altering its interaction pattern and/or increasing its cleavage by a cellular protease."
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"Although the biochemical and molecular functions of USP13 have been explored in various human cancers, including breast cancer, the oncogenic or tumor suppressor roles of USP13 in different studies has remained controversial.Here, we investigated a potential physical/functional interaction between Twist1 and USP13 in human breast cancer."
reach
"In cholangiocarcinoma, TGF-β signaling triggers the phosphorylation of CLK3, a serine/threonine kinase that directly phosphorylates USP13 at Y708 and facilitates USP13 interaction with c-Myc (Zhou et al., 2020); in GSCs, USP13 can enhance the stability through deubiquitinating c-Myc, activating purine synthesis mediated by c-Myc and inducing the tumorigenesis of GSCs (Fang et al., 2017); in hepatocellular carcinoma, knockdown of USP13 by shRNA can markedly downregulate c-Myc expression, resisting xenograft tumor growth of HCC (Huang et al., 2020)."
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"We demonstrated that (1) a recurrent Q607R somatic substitution in CLK3 was identified in 8% of 100 human CCAs, particularly in patients with CCA metastasis; (2) the expression of CLK3 was significantly up-regulated in CCA compared with matched control tissues; (3) CLK3 knockdown significantly inhibited CCA aggressiveness in vitro and in vivo; (4) gene ontology term enrichment and MS assays indicated that high CLK3 expression in CCA patients mainly regulated nucleotide metabolism, especially purine biosynthesis; (5) mechanistically, CLK3 directly phosphorylated USP13 at Y708, which promoted its binding to c-Myc, a critical purine synthesis–associated transcription factor, thereby preventing Fbxl14-mediated c-Myc ubiquitination and activating the transcription of purine metabolic genes; (6) the CCA-associated CLK3-Q607R mutant induced USP13-Y708 phosphorylation and enhanced the activity of c-Myc; (7) in turn, c-Myc transcriptionally up-regulated CLK3; (8) importantly, levels of CLK3 significantly correlated with the expression of phospho-USP13-Y708, c-Myc, and ATIC in human CCA specimens; and (9) tacrine hydrochloride was identified as a potential compound to inhibit the aberrant CLK3-enhanced CCA invasiveness."
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"Moreover, CLK3 specifically has been shown to activate the ubiquitin-specific peptidase 13 (USP13) through phosphorylation [66], and although they did not further investigate it, coIP-MS experiments published by Funnel et al. showed that the protein most significantly associated with CLK2 was no splicing factor, but USP7 [49]."
"<span class="match term0">USP13</span>, the main regulator of ovarian cancer energy metabolism, specifically deubiquitinates and stabilizes oxoglutarate dehydrogenase and ATP citrate lyase, which can catalyze fatty acid synthesis, glutaminolysis and mitochondrial respiration."
reach
"Taken together, these studies suggest that USP14 is involved in the occurrence and progression of multiple malignant tumors.Other USP family members: USP13, the main regulator of ovarian cancer energy metabolism, specifically deubiquitinates and stabilizes oxoglutarate dehydrogenase and ATP citrate lyase, which can catalyze fatty acid synthesis, glutaminolysis and mitochondrial respiration."
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"In ovarian tumors, upregulation of USP13 enhances deubiquitination and stabilization of ACLY (ATP citrate lyase) and OGDH (oxoglutarate dehydrogenase), two key enzymes that drive glutaminolysis, ATP generation, and lipid synthesis in cancer metabolism , and MCL1, a pivotal member of the antiapoptotic BCL-2 family of proteins ."
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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."
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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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"At the same time, the detection of various ubiquitination-related proteins, including PTEN ubiquitination inhibitory proteins USP7 [36] and USP13 [37] and PTEN ubiquitination-promoting protein NEDD4-1 [38], WWP1 [34], WWP2 [39] and FBXO22 [35], showed that only WWP1 and FBXO22 were significantly down-regulated, while others were not significantly changed (Fig. 4e)."
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"Although no structural information for USP13 and USP10 is currently available, the enhanced DUB activity when USP13 interacts with USP10 or when they interact with Beclin1 suggest that the interaction of USP13 and USP10 with each other or with their substrates can lead to changes in their conformation which may be critical for the catalytic activities."
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"Although no structural information for USP13 and USP10 is currently available, the enhanced DUB activity when USP13 interacts with USP10 or when they interact with Beclin1 suggest that the interaction of USP13 and USP10 with each other or with their substrates can lead to changes in their conformation which may be critical for the catalytic activities."
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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."
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"Interestingly, USP13 associates with gp78 to attenuate polyubiquitination of ubiquitin-like protein 4A (UBL4A), a part of the Bag6 complex that helps chaperone retrotranslocated ERAD substrates to the proteasome, thereby protecting the Bag6 complex from proteasomal degradation and maintaining an adequate ERAD pathway, highlighting the importance of the associated DUB activity during ERAD [ xref ]."
sparser
"Overall, the USP13-ZnF domain cannot bind to Ub to activate USP13, whereas USP13-UBA can bind, which may partially explain the reason why USP13 displays only weak basal deubiquitination enzyme activity: the binding sites of USP13 to Ub are less than that other USP members, thus providing weaker binding affinity and consequent cleavage activity towards ubiquitin chains; There possibly exists constitutive self-inhibition for full-length USP13 supported by the interaction of UBA with ZnF domain, which is hypothesized to be released by recruitment of other proteins or modification, such as phosphorylation."
sparser
"Overall, the USP13-ZnF domain cannot bind to Ub to activate USP13, whereas USP13-UBA can bind, which may partially explain the reason why USP13 displays only weak basal deubiquitination enzyme activity: the binding sites of USP13 to Ub are less than that other USP members, thus providing weaker binding affinity and consequent cleavage activity towards ubiquitin chains; There possibly exists constitutive self-inhibition for full-length USP13 supported by the interaction of UBA with ZnF domain, which is hypothesized to be released by recruitment of other proteins or modification, such as phosphorylation."
USP13 affects glycolytic process
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USP13 inhibits glycolytic process.
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13
USP13 inhibits glycolytic process. 10 / 13
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13
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"For example, overexpression of USP13 blocks the AKT signaling pathway and suppresses tumor cell proliferation, invasion, and glycolysis by upregulating PTEN, while USP13 levels are downregulated in breast, bladder, and oral squamous tumors, in correlation with PTEN levels (Fig. 3)."
USP13 activates glycolytic process.
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8
USP13 activates glycolytic process. 8 / 8
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8
reach
"Ectopically expressed K488R of METTL3 significantly promoted cell proliferation and glycolysis, while USP13 knockdown decreased cell proliferation and glycolysis with WT METTL3 rather than K488R METTL3, which indicated that mutation of K488 of METTL3 promoted cell proliferation and glycolysis and abolished USP13 depletion-induced proliferation and glycolysis suppression (Fig. 4i-n)."
reach
"Despite this, the diverse roles of autophagy in tumor biology should be explored more comprehensively.Collectively, our findings in the present study showed that USP13 promotes aerobic glycolysis and OS development by binding to, stabilizing and reducing ubiquitination and degradation of the m A writer METTL3 at K488 by removing K48-linked ubiquitin chains., which subsequently increases the m A modification of ATG5 mRNA and stabilizes it, thus promoting oncogenic autophagy."
sparser
"The isopeptidase‐independent mechanism of action proposed so far for USP13 relies on its UBA domains, which bind to ubiquitinated substrates, possibly inducing structural changes that stabilize them. xref Coincidentally, K63‐linked ubiquitin chains are required for EGFR sorting and degradation. xref This type of chains has also been reported as the preferred substrates for the USP13 UBA domains. xref We found that the UBA domains of USP13 were required for the binding to and stabilizing EGFR, as mutated UBA domains in USP13 resulted in a loss of USP13‐EGFR interaction and of EGFR stabilization."
sparser
"Thus, to identify potential inhibitory function of USP13 on Irhom2 signaling, we accordingly generated hepatocyte-specific Irhom2 -knockout (Hep Irhom2 KO) and hepatocyte-specific Usp13 and Irhom2 double deletion (Hep Usp13-Irhom2 DKO) mice (Supporting Information xref ), as indicated in Methods section."
sparser
"Thus, to identify potential inhibitory function of USP13 on Irhom2 signaling, we accordingly generated hepatocyte-specific Irhom2 -knockout (Hep Irhom2 KO) and hepatocyte-specific Usp13 and Irhom2 double deletion (Hep Usp13-Irhom2 DKO) mice (Supporting Information xref ), as indicated in Methods section."
reach
"In this study, we investigated the effect of isopeptidase T-3, also called USP13, on HMGB1, since HMGB1 ubiquitination has rarely been reported.To confirm whether USP13 binds to HMGB1, both Myc-HMGB1 and Flag-tagged USP13 (Flag-USP13) or USP10 and USP15 plasmids were overexpressed in HEK293T cells for co-immunoprecipitation."
USP13 affects inflammatory response
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19
USP13 inhibits inflammatory response.
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15
USP13 activates inflammatory response.
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4
USP13 activates USP13.
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1
8
USP13 increases the amount of USP13.
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6
reach
"To generate the LV-Usp13 or LV-shUsp13 vectors, the mouse Usp13 cDNA sequences or shRNA targeting mouse Usp13 sequences were loaded into pLenti-GFP-Puro-CMV or pLenti-U6-GFP (Addgene) to upregulate or downregulate USP13 expression in vivo experiments.2.9
Metabolic factors and serum cytokines parameters."
USP13 decreases the amount of USP13.
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2
reach
"Moreover, treatment with a proteasome inhibitor blocked the c-Myc loss caused by USP13 knockdown (not depicted), but overexpression of USP13 delayed c-Myc turnover in the presence of cycloheximide (not depicted), suggesting a critical role of USP13 in preventing proteasomal degradation of c-Myc in GSCs."
USP13 dephosphorylates USP13.
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1
reach
"Further experimental results confirmed that the USP13‐PRPF6 axis promoted the proliferation of HCC cells by modulating the AKT‐mTOR signalling pathway.In conclusion, we have demonstrated that USP13 can decrease the K48/63‐linked polyubiquitination of PRPF6, thereby stabilising this protein and promoting HCC cell proliferation via regulation of the AKT‐mTOR pathway (Figure 8C)."
reach
"Further experimental results confirmed that the USP13‐PRPF6 axis promoted the proliferation of HCC cells by modulating the AKT‐mTOR signalling pathway.In conclusion, we have demonstrated that USP13 can decrease the K48/63‐linked polyubiquitination of PRPF6, thereby stabilising this protein and promoting HCC cell proliferation via regulation of the AKT‐mTOR pathway (Figure 8C)."
reach
"This overexpression upregulated PTEN protein and downregulated AKT and FOXO1/3 phosphorylation in the MDAMB-231 cell line (XREF_FIG) which expresses moderate but detectable levels of endogenous PTEN (XREF_SUPPLEMENTARY), while knockdown of PTEN in USP13 overexpressing MDA-MB-231 cells rescued the phosphorylation of both AKT and FOXO1/3 (XREF_SUPPLEMENTARY)."
Spautin-1 decreases the amount of USP13.
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3
Spautin-1 activates USP13.
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2
reach
"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."
reach
"Our results showed that USP13 knockdown decreased the half-life of cyclin D1 and facilitated the degradation of cyclin D1 in GC cells (Fig. 4E, F), whereas enforced expression of WT USP13, but not the USP13-C345A mutant, prolonged the half-life of cyclin D1 and delayed its degradation (Fig. 4G, H)."
reach
"Consequently, ectopic expression of USP13 stabilized MITF and up-regulated MITF target genes, whereas USP13 knockdown decreased MITF protein, but not mRNA, and blocked melanoma cell proliferation.A range of additional phosphorylation events have been detected in various high-throughput proteomic screens (PhosphSitePlus, http://www.phosphosite.org/proteinAction?id=1001&showAllSites=true); however, the significance of these modifications is yet to be determined."
reach
"Further evidence showed that EMT might be the primary mechanism for the enhanced metastatic property in GC cells: USP13 and USP29 promoted TGF-β1-induced EMT through interacting with and deubiquitinating Snail, while USP3 facilitated this process by deubiquitinating SUZ12 (Wu et al. 2021; Zhang et al. 2022a, b; Qian et al. 2020)."
sparser
"Anti‐ HA (51064‐2‐AP), anti‐Flag (66008‐4‐Ig), anti‐6×His (His, 10001‐0‐AP), anti‐USP13 (16840‐1‐AP), anti‐GRP78 (11587‐1‐AP, 66574‐1‐lg), anti‐eukaryotic translation initiation factor 2‐alpha kinase 3 (PERK, 24390‐1‐AP), anti‐tight junction protein (ZO‐1, 21773‐1‐AP), anti‐Claudin‐1 (28674‐1‐AP), anti‐Occludin (27260‐1‐AP), anti‐DNA‐damage‐inducible transcript 3 (CHOP, 15204‐1‐AP), anti‐Cleaved Caspase‐3 (25128‐1‐AP), anti‐Caspase‐3 (19677‐1‐AP), anti‐activating transcription factor 4 (ATF4, 10835‐1‐AP), anti‐E‐cadherin (60335‐1‐Ig), and anti‐epithelial cell adhesion molecule (EpCAM, 21050‐1‐AP) antibodies were purchased from Proteintech (Wuhan, China)."
USP13 affects Carcinogenesis
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11
USP13 activates Carcinogenesis.
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9
USP13 inhibits Carcinogenesis.
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2
sparser
"Although no structural information for USP13 and USP10 is currently available, the enhanced DUB activity when USP13 interacts with USP10 or when they interact with Beclin1 suggest that the interaction of USP13 and USP10 with each other or with their substrates can lead to changes in their conformation which may be critical for the catalytic activities."
reach
"Although no structural information for USP13 and USP10 is currently available, the enhanced DUB activity when USP13 interacts with USP10 or when they interact with Beclin1 suggest that the interaction of USP13 and USP10 with each other or with their substrates can lead to changes in their conformation which may be critical for the catalytic activities."
sparser
"Anti‐ HA (51064‐2‐AP), anti‐Flag (66008‐4‐Ig), anti‐6×His (His, 10001‐0‐AP), anti‐USP13 (16840‐1‐AP), anti‐GRP78 (11587‐1‐AP, 66574‐1‐lg), anti‐eukaryotic translation initiation factor 2‐alpha kinase 3 (PERK, 24390‐1‐AP), anti‐tight junction protein (ZO‐1, 21773‐1‐AP), anti‐Claudin‐1 (28674‐1‐AP), anti‐Occludin (27260‐1‐AP), anti‐DNA‐damage‐inducible transcript 3 (CHOP, 15204‐1‐AP), anti‐Cleaved Caspase‐3 (25128‐1‐AP), anti‐Caspase‐3 (19677‐1‐AP), anti‐activating transcription factor 4 (ATF4, 10835‐1‐AP), anti‐E‐cadherin (60335‐1‐Ig), and anti‐epithelial cell adhesion molecule (EpCAM, 21050‐1‐AP) antibodies were purchased from Proteintech (Wuhan, China)."
USP13 affects apoptotic process
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2
10
USP13 inhibits apoptotic process.
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2
8
USP13 activates apoptotic process.
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2
sparser
"The isopeptidase‐independent mechanism of action proposed so far for USP13 relies on its UBA domains, which bind to ubiquitinated substrates, possibly inducing structural changes that stabilize them. xref Coincidentally, K63‐linked ubiquitin chains are required for EGFR sorting and degradation. xref This type of chains has also been reported as the preferred substrates for the USP13 UBA domains. xref We found that the UBA domains of USP13 were required for the binding to and stabilizing EGFR, as mutated UBA domains in USP13 resulted in a loss of USP13‐EGFR interaction and of EGFR stabilization."
"Mechanistically, <span class="match term0">USP13</span> binds to <span class="match term1">TopBP1</span> and stabilizes <span class="match term1">TopBP1</span> by deubiquitination"
reach
"Protein interaction experiments demonstrated that USP13 could co-immunoprecipitate with endogenous TopBP1, and in vitro deubiquitination enzyme experiments showed that WT-USP13 could deubiquitinate TopBP1, while CA-USP13 could not, highlighting the requirement for USP13 ubiquitination activity (Kim et al., 2021)."
reach
"USP13 has been shown to upregulate fatty acid synthase (FASN) to promote the proliferation of SCLC cells and Twist-related protein 1 (Twist1) to promote the migration and invasion of breast cancer cells, while it inhibits cell proliferation via downregulation of glycolysis in oral squamous cell carcinoma (47,48)."
sparser
"Although our research results indicate that Spautin-1 exerts anti-tumor activity dependent on the induction of PANoptosis, there are still three key limitations that need to be addressed: (1) The mechanism by which Spautin-1 regulates the USP13-ACLY axis has not been thoroughly verified. (2) The expression pattern and prognostic value of USP13 have not yet been verified in clinical samples."
USP13 affects extracellular matrix
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5
4
USP13 activates extracellular matrix.
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5
USP13 increases the amount of extracellular matrix.
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4
reach
"The study may therefore provide a molecular basis to develop new small molecules to degrade TXNIP based on TXNIP/USP13 interaction.Two independent studies demonstrated that TXNIP exhibits a pro-fibrotic property in renal fibrosis [25,26], but has been shown to exhibit an anti-fibrotic property in the liver [27]."
reach
"Interestingly, we also found that while Smad4 is translocated into the nucleus under the stimulation of TGF-β1 (10 ng/mL, 1 hour), USP13-V5 was also observed in the nucleus (Fig 6B, C), suggesting that USP13 is associated with Smad4 and the USP13/Smad4 complex is translocated into nucleus in response to TGF-β1 treatment."
sparser
"Interestingly, we also found that while Smad4 is translocated into the nucleus under the stimulation of TGF- β 1 (10 ng/mL, 1 hour), USP13-V5 was also observed in the nucleus ( xref , C), suggesting that USP13 is associated with Smad4 and the USP13/Smad4 complex is translocated into nucleus in response to TGF- β 1 treatment."
sparser
"A coimmunoprecipitation assay was performed in Flag-tagged Raf1 (Flag-Raf1)-overexpressing 46C mESCs carrying the HA or HA-USP13 transgene with a Flag antibody-affinity gel, which was used to bind the Flag fusion protein for immunoprecipitation analysis, to determine whether USP13 interacts with Raf1 ( xref A )."
reach
"Mechanistically, we demonstrate that USP13 physically interacts with, deubiquitinates, and stabilizes serine/threonine kinase Raf1 and thereby sustains Raf1 protein at the posttranslational level to activate the FGF/MEK/ERK prodifferentiation signaling pathway in naive mouse ESCs."
USP13 affects cell cycle
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1
7
USP13 activates cell cycle.
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1
6
USP13 activates cell cycle. 7 / 7
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1
6
reach
"In addition, reconstitution of WT USP13, but not the T196A mutant, fully rescued the foci formation of the BRCA1-A complex, DNA repair and cell cycle checkpoint in USP13 deficient cells and reversed hypersensitivity to cisplatin or olaparib induced by USP13 deficiency (XREF_FIG and XREF_SUPPLEMENTARY)."
USP13 inhibits cell cycle.
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1
USP13 inhibits cell cycle. 1 / 1
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1
sparser
"Although the experimental results showed that USP13-UBA could bind ubiquitin, USP13 still exhibited only weak deubiquitination enzyme activity, which is incompatible with the findings that USP13 can deubiquitinate various important substrates implicated in disease and tumor development ( xref ; xref )."
sparser
"Overall, the USP13-ZnF domain cannot bind to Ub to activate USP13, whereas USP13-UBA can bind, which may partially explain the reason why USP13 displays only weak basal deubiquitination enzyme activity: the binding sites of USP13 to Ub are less than that other USP members, thus providing weaker binding affinity and consequent cleavage activity towards ubiquitin chains; There possibly exists constitutive self-inhibition for full-length USP13 supported by the interaction of UBA with ZnF domain, which is hypothesized to be released by recruitment of other proteins or modification, such as phosphorylation."
reach
"Further experimental results confirmed that the USP13‐PRPF6 axis promoted the proliferation of HCC cells by modulating the AKT‐mTOR signalling pathway.In conclusion, we have demonstrated that USP13 can decrease the K48/63‐linked polyubiquitination of PRPF6, thereby stabilising this protein and promoting HCC cell proliferation via regulation of the AKT‐mTOR pathway (Figure 8C)."
sparser
"Although the experimental results showed that USP13-UBA could bind ubiquitin, USP13 still exhibited only weak deubiquitination enzyme activity, which is incompatible with the findings that USP13 can deubiquitinate various important substrates implicated in disease and tumor development ( xref ; xref )."
sparser
"Overall, the USP13-ZnF domain cannot bind to Ub to activate USP13, whereas USP13-UBA can bind, which may partially explain the reason why USP13 displays only weak basal deubiquitination enzyme activity: the binding sites of USP13 to Ub are less than that other USP members, thus providing weaker binding affinity and consequent cleavage activity towards ubiquitin chains; There possibly exists constitutive self-inhibition for full-length USP13 supported by the interaction of UBA with ZnF domain, which is hypothesized to be released by recruitment of other proteins or modification, such as phosphorylation."
USP13 affects AE
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7
sparser
"To determine whether USP13 contributes to malignant phenotypes, we established HCT116 and HCT15 cell lines stably overexpressing wild-type USP13 (USP13-WT) or its catalytically inactive mutant USP13-AE (C345A/M664/739E) (Fig. xref a), and generated USP13-knockout RKO and SW48 cells via CRISPR/Cas9 (Fig. xref b)."
AE affects USP13
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7
sparser
"To determine whether USP13 contributes to malignant phenotypes, we established HCT116 and HCT15 cell lines stably overexpressing wild-type USP13 (USP13-WT) or its catalytically inactive mutant USP13-AE (C345A/M664/739E) (Fig. xref a), and generated USP13-knockout RKO and SW48 cells via CRISPR/Cas9 (Fig. xref b)."
Barium(2+) affects USP13
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6
Barium(2+) activates USP13.
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3
Barium(2+) inhibits USP13.
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2
Barium(2+) decreases the amount of USP13.
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1
Barium(2+) decreases the amount of USP13. 1 / 1
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1
USP13 affects cell growth
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6
USP13 affects Stomach Neoplasms
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6
USP13 activates Stomach Neoplasms.
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4
USP13 deubiquitinates Stomach Neoplasms.
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2
USP13 deubiquitinates Stomach Neoplasms. 2 / 2
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2
sparser
"The antagonistic actions between ubiquitin ligases and DUBs are responsible for protein homeostasis as exemplified that USP13-FBXL14 regulated reversible ubiquitination of c-Myc in glioblastoma stem cells [ xref ], and USP15-SMURF2 cooperatively modulated TGF-β receptor in glioblastoma [ xref ]."
sparser
"The antagonistic actions between ubiquitin ligases and DUBs are responsible for protein homeostasis as exemplified that USP13-FBXL14 regulated reversible ubiquitination of c-Myc in glioblastoma stem cells [ xref ], and USP15-SMURF2 cooperatively modulated TGF-β receptor in glioblastoma [ xref ]."
P97 affects USP13
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5
sparser
"Compared to the control (cells transfected with an empty vector), expression of several UBX domain-containing p97 cofactors including ASPL, SAK1, and UbxD1 reduced the p97-USP13 interaction ( xref , lanes 3, 5, 7 vs lane 1), suggesting that these factors may compete with USP13 for p97 binding."
USP13 affects p97
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5
sparser
"Compared to the control (cells transfected with an empty vector), expression of several UBX domain-containing p97 cofactors including ASPL, SAK1, and UbxD1 reduced the p97-USP13 interaction ( xref , lanes 3, 5, 7 vs lane 1), suggesting that these factors may compete with USP13 for p97 binding."
USP13 affects cellular senescence
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5
USP13 affects USP
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5
reach
"Our study reveals a new regulatory mechanism by which the USP13‐PARP1 complex can be activated to promote MM progression by enhancing DDR, contributing to a comprehensive understanding of the regulatory spectrum governed by USP13.There has been a growing interest in bioactive compounds derived from Traditional Chinese Medicine Materials (TCMMs), and their potential to combat MM has been extensively studied [39]."
USP13 affects Interferon
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1
4
USP13 affects ERAD
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1
4
reach
"Our study reveals a new regulatory mechanism by which the USP13‐PARP1 complex can be activated to promote MM progression by enhancing DDR, contributing to a comprehensive understanding of the regulatory spectrum governed by USP13.There has been a growing interest in bioactive compounds derived from Traditional Chinese Medicine Materials (TCMMs), and their potential to combat MM has been extensively studied [39]."
USP affects USP13
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5
reach
"Our study reveals a new regulatory mechanism by which the USP13‐PARP1 complex can be activated to promote MM progression by enhancing DDR, contributing to a comprehensive understanding of the regulatory spectrum governed by USP13.There has been a growing interest in bioactive compounds derived from Traditional Chinese Medicine Materials (TCMMs), and their potential to combat MM has been extensively studied [39]."
Ubiquitin-proteasome affects USP13
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4
MiR-130b/301b affects USP13
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4
USP13 affects signal transduction
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4
USP13 inhibits signal transduction.
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2
USP13 activates signal transduction.
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2
USP13 affects pyroptosis
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4
USP13 affects glioblastoma multiforme cancer stem cell
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4
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4
USP13 affects cell migration
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4
USP13 affects UBL
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4
USP13 affects NASH
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4
reach
"Given the close-knit correlation of IRHOM2 deactivation with ubiquitin-associated domains activity of USP13, to thoroughly study whether USP13–IRHOM2 interaction is necessary for the inhibitory function of USP13 against NASH progression, AAV8-TBG-loaded WT full-length Usp13 sequences vectors (AAV-TBG-Usp13) and AAV8-TBG-loaded Usp13 with UBA1/2 domain deletion vectors (AAV-TBG-Usp13 (ΔUBA)) was generated and used again to further explore the influence of USP13 with UBA1/2 mutants on HFHC-induced NASH pathologies in vivo (Fig. S18N)."
USP13 affects DNA Damage
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4
USP13 inhibits DNA Damage.
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2
USP13 inhibits DNA Damage. 2 / 2
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2
USP13 activates DNA Damage.
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2
USP13 affects Cell Survival
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2
2
sparser
"Given the involvement of diverse physiological processes in ferroptosis, gaining a comprehensive understanding of the role of the USP13-ATG7 axis in chicken follicle growth and development can provide valuable insights into molecular-assisted breeding strategies and serve as a foundation for enhancing poultry yield."
USP13 affects AAV9
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4
sparser
"The results revealed a pronounced increase in GPX4 and SLC7A11, along with a significant decrease in PTGS2, TNF and IL-6, in the AAV9-USP13 oe mice compared to the AAV9-Ctrl mice, while there was no substantial discrepancy in the expression of cleaved caspase-3. ( xref B through 7D and xref through S14D)."
UBL affects USP13
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4
reach
"Interestingly, we also found that while Smad4 is translocated into the nucleus under the stimulation of TGF-β1 (10 ng/mL, 1 hour), USP13-V5 was also observed in the nucleus (Fig 6B, C), suggesting that USP13 is associated with Smad4 and the USP13/Smad4 complex is translocated into nucleus in response to TGF-β1 treatment."
sparser
"Interestingly, we also found that while Smad4 is translocated into the nucleus under the stimulation of TGF- β 1 (10 ng/mL, 1 hour), USP13-V5 was also observed in the nucleus ( xref , C), suggesting that USP13 is associated with Smad4 and the USP13/Smad4 complex is translocated into nucleus in response to TGF- β 1 treatment."
sparser
"A coimmunoprecipitation assay was performed in Flag-tagged Raf1 (Flag-Raf1)-overexpressing 46C mESCs carrying the HA or HA-USP13 transgene with a Flag antibody-affinity gel, which was used to bind the Flag fusion protein for immunoprecipitation analysis, to determine whether USP13 interacts with Raf1 ( xref A )."
reach
"Mechanistically, we demonstrate that USP13 physically interacts with, deubiquitinates, and stabilizes serine/threonine kinase Raf1 and thereby sustains Raf1 protein at the posttranslational level to activate the FGF/MEK/ERK prodifferentiation signaling pathway in naive mouse ESCs."
sparser
"Given the involvement of diverse physiological processes in ferroptosis, gaining a comprehensive understanding of the role of the USP13-ATG7 axis in chicken follicle growth and development can provide valuable insights into molecular-assisted breeding strategies and serve as a foundation for enhancing poultry yield."
AAV9 affects USP13
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4
sparser
"The results revealed a pronounced increase in GPX4 and SLC7A11, along with a significant decrease in PTGS2, TNF and IL-6, in the AAV9-USP13 oe mice compared to the AAV9-Ctrl mice, while there was no substantial discrepancy in the expression of cleaved caspase-3. ( xref B through 7D and xref through S14D)."
Ubiquitin-proteasome system affects USP13
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3
USP13 affects α-synuclein
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3
reach
"Here, it was shown that USP13 negatively regulates Parkin ubiquitination, function, and solubility (Figure 5), negatively regulates the level, ubiquitination, and clearance of α-synuclein, and regulates proteasome activity independently of Parkin, which affects dopaminergic neuronal viability and motor performances in animal models."
USP13 affects miR-301b-3p
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3
USP13 affects ferroptosis
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3
USP13 affects cell death
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3
USP13 affects barium(2+)
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3
USP13 affects Proteasome
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3
USP13 affects Glioblastoma
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1
USP13 activates Glioblastoma. 1 / 3
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1
sparser
"First, USP13 binds to eIF5B and enhances its interaction with SQSTM1/P62, promoting autophagy-lysosomal degradation of eIF5B. Second, previous studies show the functions of USP13 in SQSTM1/P62–USP13 stabilizes SQSTM1/P62 through depubiquitination, thus promoting the oligomerization of SQSTM1/P62 [ xref ], augmenting SQSTM1/P62’s substrate recruitment."
USP13 affects Deubiquitinase
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3
USP13 activates Deubiquitinase. 3 / 3
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3
reach
"As shown in Fig. 5i, j, USP13 overexpression significantly suppressed IκBα degradation while USP13 downregulation accelerated IκBα degradation.USP13 is a deubiquitinase (DUB) and regulates IκBα stability, therefore, analyses were performed to explore if USP13 regulates IκBα ubiquitination."
reach
"As shown in Fig. 5i, j, USP13 overexpression significantly suppressed IκBα degradation while USP13 downregulation accelerated IκBα degradation.USP13 is a deubiquitinase (DUB) and regulates IκBα stability, therefore, analyses were performed to explore if USP13 regulates IκBα ubiquitination."
USP13 affects Beclin1 subunit
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3
reach
"We treated TBEV infected neuroblastoma cells with rapamycin (inducer of autophagy, as inhibition of mTOR mimics cellular starvation by blocking signals required for cell growth and proliferation), and spautin-1 (highly specific and potent autophagy inhibitor in mammalian cells, which promotes the degradation of Vps34 PI3 kinase complexes by inhibiting two ubiquitin specific peptidases, USP10 and USP13 that target the Beclin1 subunit of Vps34 complexes) and investigated the effect of the treatment of TBEV growth."
USP13 affects Aloe emodin
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3
Aloe emodin binds USP13. 3 / 3
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sparser
"Given previous findings that USP13 stabilizes HIF-1α through its deubiquitinase activity, stable USP13-AE overexpressing cells exhibited comparable proliferation rates to control groups (Fig. S4A), suggesting that USP13 promotes CRC cell proliferation in a deubiquitinase activity-dependent manner."
Spautin‐1 affects USP13
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3
sparser
"First, USP13 binds to eIF5B and enhances its interaction with SQSTM1/P62, promoting autophagy-lysosomal degradation of eIF5B. Second, previous studies show the functions of USP13 in SQSTM1/P62–USP13 stabilizes SQSTM1/P62 through depubiquitination, thus promoting the oligomerization of SQSTM1/P62 [ xref ], augmenting SQSTM1/P62’s substrate recruitment."
Aloe emodin affects USP13
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Aloe emodin binds USP13. 3 / 3
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3
sparser
"Given previous findings that USP13 stabilizes HIF-1α through its deubiquitinase activity, stable USP13-AE overexpressing cells exhibited comparable proliferation rates to control groups (Fig. S4A), suggesting that USP13 promotes CRC cell proliferation in a deubiquitinase activity-dependent manner."
Valproic acid affects USP13
2
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Phenylmercury acetate affects USP13
2
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MiR-145-5p affects USP13
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2
Imidazolide affects USP13
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1
1
Doxycycline affects USP13
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2
Bisphenol A affects USP13
2
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Benzo[a]pyrene affects USP13
2
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All-trans-retinoic acid affects USP13
2
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USP13 affects tumor growth
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2
USP13 affects stabilization TLR4
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2
USP13 affects stabilisation Mcl-1
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2
USP13 affects regulation of cell cycle
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USP13 inhibits regulation of cell cycle. 2 / 2
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2
USP13 affects recruitment
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1
1
USP13 affects pathogenesis
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USP13 affects navitoclax
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USP13 activates navitoclax. 2 / 2
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USP13 affects metabolic process
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2
USP13 affects immune response
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2
USP13 affects half-life MITF-M
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2
USP13 affects glucose import
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2
USP13 inhibits glucose import. 2 / 2
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2
USP13 affects glioma stem cells
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2
USP13 affects autophagy-related protein 5
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2
USP13 affects Virus Replication
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USP13 activates Virus Replication. 2 / 2
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2
eidos
"Our results demonstrate that USP13 is hijacked to maintain nsp13 expression and the inhibitory role of nsp13 in regulating type I IFN production , and USP13 inhibitor could be employed to suppress virus replication by targeting nsp13 for degradation thereby disrupting its inhibitory role in regulating type I IFN production ."
eidos
"Moreover , depletion of USP13 or treatment with USP13 inhibitor relieves the inhibitory role of nsp13 for type I IFN response and suppresses virus replication in host cells , suggesting that USP13 inhibitor could be employed to suppress virus replication by targeting nsp13 for degradation ."
USP13 affects TCRalpha
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2
USP13 affects Reactive Oxygen Species
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2
reach
"Here, it was shown that USP13 negatively regulates Parkin ubiquitination, function, and solubility (Figure 5), negatively regulates the level, ubiquitination, and clearance of α-synuclein, and regulates proteasome activity independently of Parkin, which affects dopaminergic neuronal viability and motor performances in animal models."
USP13 affects Osteosarcoma
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2
USP13 affects MITF-M protein
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2
reach
"Except for temsirolimus (mTOR inhibitor), specific inhibitors of kinases ULK1 and ULK1/ULK2 (SBI-0206965 and MRT68921 dihydrochloride) as well as hydrolases USP10/USP13 (Spautin-1) involved in the process of autophagy decreased LDH release to 138%, 141%, and 134% of the control, respectively (Fig. 1a)."
USP13 affects L02
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2
USP13 affects IRHOM2
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2
USP13 affects Helicase nsp13
2
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USP13 affects E3_Ub_ligase
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2
sparser
"Mass spectrometry, immunoprecipitation, and in vitro functional assays were conducted to explore the interaction between USP13 and WISP1 and to assess the effects of USP13 downregulation on cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and apoptosis."
reach
"Mass spectrometry, immunoprecipitation, and in vitro functional assays were conducted to explore the interaction between USP13 and WISP1 and to assess the effects of USP13 downregulation on cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and apoptosis."
UBL affects BAG6
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2
reach
"The study may therefore provide a molecular basis to develop new small molecules to degrade TXNIP based on TXNIP/USP13 interaction.Two independent studies demonstrated that TXNIP exhibits a pro-fibrotic property in renal fibrosis [25,26], but has been shown to exhibit an anti-fibrotic property in the liver [27]."
RHBDF2 affects L02
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2
Particulate Matter affects USP13
2
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L02 affects USP13
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2
IRHOM2 affects USP13
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2
Hep KO mice affects USP13
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2
Helicase nsp13 affects USP13
2
|
sparser
"Mass spectrometry, immunoprecipitation, and in vitro functional assays were conducted to explore the interaction between USP13 and WISP1 and to assess the effects of USP13 downregulation on cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and apoptosis."
reach
"Mass spectrometry, immunoprecipitation, and in vitro functional assays were conducted to explore the interaction between USP13 and WISP1 and to assess the effects of USP13 downregulation on cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and apoptosis."
reach
"Specifically, Esposito et al. found that Aurora kinase B, crucial for mitosis, phosphorylates USP13 at the serine 114 and that this phosphorylation enhances the interaction of both proteins, thereby maintaining the stability of Aurora kinase B. Intriguingly, USP13 stabilizes Aurora kinase B by modulating its ubiquitination, a process that occurs independently of its DUB activity."
2-methoxy-17beta-estradiol affects USP13
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2
Perfluorooctanesulfonamide affects USP13
1
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Isobutanol affects USP13
1
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Indometacin affects USP13
1
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Hsa-miR-548f-5p affects USP13
1
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Hsa-miR-539-3p affects USP13
1
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Hsa-miR-3118 affects USP13
1
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Adeno-associated virus serotype-8 affects USP13
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1
reach
"In the indicated experiments, the conditional overexpression of Usp13 in hepatocytes (Hep OE) were triggered by injection of adeno-associated virus serotype-8 (AAV8)-thyroxine-binding globulin promoter (TBG)-recombinase Cre vector (AAV8-TBG-Cre) via intravenous injection and then determined by immunoblotting assay."
1
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USP13 affects tumor initiation
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1
USP13 affects transporter-1
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1
USP13 affects stemness-related protein
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1
USP13 affects sensitivity cervical cancer cells BH3 mimetic ABT-263
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1
USP13 affects pathways
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1
USP13 affects p-RPA32 S33 staining
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1
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1
USP13 activates negative regulation of apoptotic process. 1 / 1
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1
USP13 affects localization
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1
USP13 activates localization. 1 / 1
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1
USP13 affects hiPSCs
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1
USP13 affects half-life mutant protein NSCLC cells
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1
USP13 affects growth metastasis mice
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1
USP13 affects cervical cancer cell
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1
USP13 affects active caspase
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1
USP13 affects abundance anti-apoptotic protein MCL1 lung
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1
USP13 affects UBA domains
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1
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1
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1
USP13 inhibits Intervertebral Disc Degeneration. 1 / 1
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1
USP13 affects H460
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1
USP13 affects DNA damage checkpoint signaling
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1
USP13 activates DNA damage checkpoint signaling. 1 / 1
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1
USP13 affects B-Lymphocytes
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1
USP13 activates B-Lymphocytes. 1 / 1
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1
USP13 affects AKT inhibitors
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1
USP13 affects 135b
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1
USP-Y708F affects USP13
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1
UBA domains affects USP13
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1
Reperfusion Injury affects USP13
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1
Reperfusion Injury inhibits USP13. 1 / 1
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1
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1
NF-kB p65 affects USP13
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1
JNK inhibitor affects USP13
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1
Infections affects USP13
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1
Infections increases the amount of USP13. 1 / 1
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1
H460 affects VIM
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1