Breaking the chains: deubiquitylating enzyme specificity begets function
Top Cited Papers
- 7 February 2019
- journal article
- review article
- Published by Springer Science and Business Media LLC in Nature Reviews Molecular Cell Biology
- Vol. 20 (6), 338-352
- https://doi.org/10.1038/s41580-019-0099-1
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.Keywords
This publication has 223 references indexed in Scilit:
- OTU Deubiquitinases Reveal Mechanisms of Linkage Specificity and Enable Ubiquitin Chain Restriction AnalysisCell, 2013
- OTULIN Antagonizes LUBAC Signaling by Specifically Hydrolyzing Met1-Linked PolyubiquitinCell, 2013
- A Conserved Deubiquitinating Enzyme Controls Cell Growth by Regulating RNA Polymerase I StabilityCell Reports, 2012
- OTUB1 Co-opts Lys48-Linked Ubiquitin Recognition to Suppress E2 Enzyme FunctionMolecular Cell, 2012
- Regulation of Ubiquitin Chain Initiation to Control the Timing of Substrate DegradationMolecular Cell, 2011
- The Mechanism of Linkage-Specific Ubiquitin Chain Elongation by a Single-Subunit E2Cell, 2011
- Requirement of ATM-Dependent Monoubiquitylation of Histone H2B for Timely Repair of DNA Double-Strand BreaksMolecular Cell, 2011
- Human USP3 Is a Chromatin Modifier Required for S Phase Progression and Genome StabilityCurrent Biology, 2007
- A Histone H2A Deubiquitinase Complex Coordinating Histone Acetylation and H1 Dissociation in Transcriptional RegulationMolecular Cell, 2007
- Solution Structure of the Ubp-M BUZ Domain, a Highly Specific Protein Module that Recognizes the C-terminal Tail of Free UbiquitinJournal of Molecular Biology, 2007