Breaking the chains: deubiquitylating enzyme specificity begets function

Clague, Michael J ORCID: 0000-0003-3355-9479, Urbe, Sylvie ORCID: 0000-0003-4735-9814 and Komander, David (2019) Breaking the chains: deubiquitylating enzyme specificity begets function. NATURE REVIEWS MOLECULAR CELL BIOLOGY, 20 (6). pp. 338-352.

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Abstract

The deubiquitylating enzymes (DUBs, also known as deubiquitylases or deubiquitinases) maintain the dynamic state of the cellular ubiquitome by releasing conjugated ubiquitin from proteins. In light of the many cellular functions of ubiquitin, DUBs occupy key roles in almost all aspects of cell behaviour. Many DUBs show selectivity for particular ubiquitin linkage types or positions within ubiquitin chains. Others show chain-type promiscuity but can select a distinct palette of protein substrates via specific protein-protein interactions established through binding modules outside of the catalytic domain. The ubiquitin chain cleavage mode or chain linkage specificity has been related directly to biological functions. Examples include regulation of protein degradation and ubiquitin recycling by the proteasome, DNA repair pathways and innate immune signalling. DUB cleavage specificity is also being harnessed for analysis of ubiquitin chain architecture that is assembled on specific proteins. The recent development of highly specific DUB inhibitors heralds their emergence as a new class of therapeutic targets for numerous diseases.

Item Type:	Article
Uncontrolled Keywords:	Animals, Humans, Proteasome Endopeptidase Complex, Ubiquitin, Signal Transduction, Substrate Specificity, Ubiquitination, Proteolysis, Deubiquitinating Enzymes
Depositing User:	Symplectic Admin
Date Deposited:	14 Mar 2019 08:50
Last Modified:	19 Jan 2023 00:57
DOI:	10.1038/s41580-019-0099-1
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3034202