共 201 条
Mechanisms of Deubiquitinase Specificity and Regulation
被引:775
作者:

Mevissen, Tycho E. T.
论文数: 0 引用数: 0
h-index: 0
机构:
MRC, Mol Biol Lab, Cambridge CB2 0QH, England MRC, Mol Biol Lab, Cambridge CB2 0QH, England

Komander, David
论文数: 0 引用数: 0
h-index: 0
机构:
MRC, Mol Biol Lab, Cambridge CB2 0QH, England MRC, Mol Biol Lab, Cambridge CB2 0QH, England
机构:
[1] MRC, Mol Biol Lab, Cambridge CB2 0QH, England
来源:
ANNUAL REVIEW OF BIOCHEMISTRY, VOL 86
|
2017年
/
86卷
基金:
英国医学研究理事会;
关键词:
ubiquitin code;
linkage specificity;
allosteric regulation;
substrate-assisted catalysis;
posttranslational modification;
deubiquitinase;
POLYGLUTAMINE DISEASE PROTEIN;
KAPPA-B ACTIVATION;
STRUCTURAL BASIS;
UBIQUITIN CHAINS;
HISTONE H2B;
LINEAR POLYUBIQUITIN;
CRYSTAL-STRUCTURE;
MOLECULAR-BASIS;
CYLD USP;
ENZYME;
D O I:
10.1146/annurev-biochem-061516-044916
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Protein ubiquitination is one of the most powerful posttranslational modifications of proteins, as it regulates a plethora of cellular processes in distinct manners. Simple monoubiquitination events coexist with more complex forms of polyubiquitination, the latter featuring many different chain architectures. Ubiquitin can be subjected to further posttranslational modifications (e.g., phosphorylation and acetylation) and can also be part of mixed polymers with ubiquitin-like modifiers such as SUMO (small ubiquitin-related modifier) or NEDD8 (neural precursor cell expressed, developmentally downregulated 8). Together, cellular ubiquitination events form a sophisticated and versatile ubiquitin code. Deubiquitinases (DUBs) reverse ubiquitin signals with equally high sophistication. In this review, we conceptualize the many layers of specificity that DUBs encompass to control the ubiquitin code and discuss examples in which DUB specificity has been understood at the molecular level. We further discuss the many mechanisms of DUB regulation with a focus on those that modulate catalytic activity. Our review provides a framework to tackle lingering questions in DUB biology.
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页码:159 / 192
页数:34
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