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去泛素化酶与疾病

Deubiquitylating enzymes and disease.

作者信息

Singhal Shweta, Taylor Matthew C, Baker Rohan T

机构信息

Ubiquitin Laboratory, Division of Molecular Bioscience, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT 0200, Australia.

出版信息

BMC Biochem. 2008 Oct 21;9 Suppl 1(Suppl 1):S3. doi: 10.1186/1471-2091-9-S1-S3.

DOI:10.1186/1471-2091-9-S1-S3
PMID:19007433
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2582804/
Abstract

Deubiquitylating enzymes (DUBs) can hydrolyze a peptide, amide, ester or thiolester bond at the C-terminus of UBIQ (ubiquitin), including the post-translationally formed branched peptide bonds in mono- or multi-ubiquitylated conjugates. DUBs thus have the potential to regulate any UBIQ-mediated cellular process, the two best characterized being proteolysis and protein trafficking. Mammals contain some 80-90 DUBs in five different subfamilies, only a handful of which have been characterized with respect to the proteins that they interact with and deubiquitylate. Several other DUBs have been implicated in various disease processes in which they are changed by mutation, have altered expression levels, and/or form part of regulatory complexes. Specific examples of DUB involvement in various diseases are presented. While no specific drugs targeting DUBs have yet been described, sufficient functional and structural information has accumulated in some cases to allow their rapid development. PUBLICATION HISTORY : Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com).

摘要

去泛素化酶(DUBs)能够水解泛素(UBIQ)C末端的肽键、酰胺键、酯键或硫酯键,包括单泛素化或多泛素化共轭物中翻译后形成的分支肽键。因此,DUBs有可能调节任何由泛素介导的细胞过程,其中研究得最透彻的两个过程是蛋白水解和蛋白质运输。哺乳动物在五个不同的亚家族中大约含有80 - 90种DUBs,其中只有少数几种在与其相互作用并去泛素化的蛋白质方面得到了表征。其他几种DUBs与各种疾病过程有关,在这些疾病中它们会因突变而发生变化、表达水平改变,和/或成为调节复合物的一部分。文中给出了DUBs参与各种疾病的具体例子。虽然尚未描述针对DUBs的特异性药物,但在某些情况下已经积累了足够的功能和结构信息以使其快速研发。发表历史:转载自Current BioData的靶向蛋白质数据库(TPdb;http://www.targetedproteinsdb.com)。

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本文引用的文献

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Ubiquitin chains are remodeled at the proteasome by opposing ubiquitin ligase and deubiquitinating activities.泛素链在蛋白酶体处通过相反的泛素连接酶和去泛素化活性进行重塑。
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Impaired regulation of NF-kappaB and increased susceptibility to colitis-associated tumorigenesis in CYLD-deficient mice.CYLD基因缺陷小鼠中NF-κB调控受损及对结肠炎相关肿瘤发生的易感性增加。
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Critical role for Daxx in regulating Mdm2.Daxx在调控Mdm2中起关键作用。
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