功能 |
Hydrolase that removes conjugated ubiquitin from target proteins and regulates various pathways such as the TGF-beta receptor signaling and NF-kappa-B pathways. Acts as a key regulator of TGF-beta receptor signaling pathway, but the precise mechanism is still unclear: according to a report, acts by promoting deubiquitination of monoubiquitinated R-SMADs (SMAD1, SMAD2 and/or SMAD3), thereby alleviating inhibition of R-SMADs and promoting activation of TGF-beta target genes (PubMed:21947082). According to another reports, regulates the TGF-beta receptor signaling pathway by mediating deubiquitination and stabilization of TGFBR1, leading to an enhanced TGF-beta signal (PubMed:22344298). Able to mediate deubiquitination of monoubiquitinated substrates as well as 'Lys-48'-linked polyubiquitin chains, protecting them against proteasomal degradation. May also regulate gene expression and/or DNA repair through the deubiquitination of histone H2B (PubMed:24526689). Acts as an associated component of COP9 signalosome complex (CSN) and regulates different pathways via this association: regulates NF-kappa-B by mediating deubiquitination of NFKBIA and deubiquitinates substrates bound to VCP. Protects APC and human papillomavirus type 16 protein E6 against degradation via the ubiquitin proteasome pathway.
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總結(jié) |
The ubiquitin (Ub) pathway involves three sequential enzymatic steps that facilitate the conjugation of Ub and Ub-like molecules to specific protein substrates. Through the use of a wide range of enzymes that can add or remove ubiquitin, the Ub pathway controls many intracellular processes such as signal transduction, transcriptional activation and cell cycle progression. USP15 (ubiquitin specific peptidase 15), also known as UNPH4, is a member of the peptidase C19 family of proteins. Expressed in kidney, liver, placenta, ovary, lung, thymus, heart and skeletal muscle, USP15 localizes to the cytoplasm and the nucleus, contains one DUSP domain and functions as a deubiquitinating enzyme that cleaves ubiquitin residues from both ubiquitinylated proteins and ubiquitin-fused precursors, thereby saving these proteins from proteasomal degradation. Via its DUSP domain, USP15 plays a role in the regulation of the COP9 signalosome (CSN) complex. Three isoforms exist for USP15 due to alternative splicing events.
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