- USP10provided by HGNC
- Official Full Name
- ubiquitin specific peptidase 10
- Also known as
- UBPO
- Summary
- Ubiquitin is a highly conserved protein that is covalently linked to other proteins to regulate their function and degradation. This gene encodes a member of the ubiquitin-specific protease family of cysteine proteases. The enzyme specifically cleaves ubiquitin from ubiquitin-conjugated protein substrates. The protein is found in the nucleus and cytoplasm. It functions as a co-factor of the DNA-bound androgen receptor complex, and is inhibited by a protein in the Ras-GTPase pathway. The human genome contains several pseudogenes similar to this gene. Several transcript variants, some protein-coding and others not protein-coding, have been found for this gene. [provided by RefSeq, Jan 2013]
- Expression Ubiquitous expression in placenta (RPKM 15.2), lymph node (RPKM 13.4) and 25 other tissues See more
- Deubiquitinase USP10 regulates Notch signaling in the endothelium. Lim R, et al. Science, 2019 Apr 12. PMID 30975888l Notch signaling is a core patterning module for vascular morphogenesis that codetermines the sprouting behavior of endothelial cells (ECs). Tight quantitative and temporal control of Notch activity is essential for vascular development, yet the details of Notch regulation in ECs are incompletely understood. 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. Accordingly, inactivation of USP10 reduced NICD1 abundance and stability and diminished Notch-induced target gene expression in ECs. In mice, the loss of endothelial Usp10 increased vessel sprouting and partially restored the patterning defects caused by ectopic expression of NICD1. Thus, USP10 functions as an NICD1 deubiquitinase that fine-tunes endothelial Notch responses during angiogenic sprouting.
- The deubiquitylase USP10 regulates integrin β1 and β5 and fibrotic wound healing. Gillespie SR, et al. J Cell Sci, 2017 Oct 15. PMID 28851806, Free PMC Article
- USP10 Expression in Normal Adrenal Gland and Various Adrenal Tumors. Zeng Z, et al. Endocr Pathol, 2015 Dec. PMID 26555087
- USP10 antagonizes c-Myc transcriptional activation through SIRT6 stabilization to suppress tumor formation. Lin Z, et al. Cell Rep, 2013 Dec 26. PMID 24332849, Free PMC Article
- Over-expression of genes and proteins of ubiquitin specific peptidases (USPs) and proteasome subunits (PSs) in breast cancer tissue observed by the methods of RFDD-PCR and proteomics. Deng S, et al. Breast Cancer Res Treat, 2007 Jul. PMID 17004105
GeneRIFs: Gene References Into Functions
- USP10 silencing demonstrated the inverse effects, and these effects induced by USP10 silencing were significantly blocked by EGF. USP10 overexpression promoted Raf-1 protein expression, but not mRNA expression, through deubiquitination... 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
- USP10 functions as an NOTCH1 intracellular domain (NICD1) deubiquitinase that fine-tunes endothelial Notch responses during angiogenic sprouting.
- USP10 inhibits hepatic steatosis, insulin resistance, and inflammation through Sirt6.
- USP10 was expressed primarily in the cytoplasm of prostate cancer tissues. High levels of USP10 expression were strongly correlated with high levels of AR, G3BP2, and p53 in the cytoplasm. High expression of USP10 was significantly associated with poor prognosis of patients with prostate cancer.
- By using a genome wide siRNA screen for deubiquitinating enzymes, we identified USP10 as a deubiquitinase for Slug in cancer cells. USP10 interacts with Slug and mediates its degradation by the proteasome. Importantly, USP10 is concomitantly highly expressed with Slug in cancer biopsies.
- Loss of USP10 expression is associated with small intestinal adenocarcinoma.
- One of the USP10 targets is TP53. Wildtype TP53 is usually rescued from proteasomal degradation by USP10. As most KMT2A leukemias display wildtype p53 alleles, one might argue that the disruption of an USP10 allele can be classified as a pro-oncogenic event.
- Deubiquitylase USP10 interacts with RNF168 and TOP2alpha, and restrains ubiquitylation of TOP2alpha as well as its chromatin binding.
- USP10 directly interacted with and stabilized PTEN via deubiquitination. Mol Cell Biochem. 2018 Apr;441(1-2):1-7. doi: 10.1007/s11010-017-3170-2. Epub 2017 Aug 29. USP10 inhibits lung cancer cell growth and invasion by upregulating PTEN. Sun J1, Li T1, Zhao Y1, Huang L1, Sun H1, Wu H1, Jiang X2.To determine the potential tumor suppressor functions of ubiquitin-specific protease 10 (USP10) in lung cancer and elucidate underlying molecular mechanism. The relative expression of USP10 was determined by real-time PCR and immunoblotting. The inhibitory effect of USP10 on tumor growth was demonstrated on allograft mice with Lewis carcinoma cell inoculation. The relative cell proliferation was measured with Cell Counting Kit-8 (CCK-8). The invasive capacity was evaluated by transwell assay. The interaction between USP10 and Phosphatase And Tensin Homolog (PTEN) was examined by co-immunoprecipitation. Ubiquitination/deubiquitination was analyzed by immunoprecipitation followed by immunoblotting. USP10 was down-regulated in lung cancer. Knockdown of USP10 promotes tumor growth and invasion both in vitro and in vivo. We further demonstrated that USP10 directly interacted with and stabilized PTEN via deubiquitination. The pro-cancerous effect of USP10 deficiency was abolished by re-introduction of PTEN. We suggested a tumor suppressor function of USP10 in lung cancer via deubiquitinating and stabilizing PTEN.
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