OTU deubiquitinases reveal mechanisms of linkage specificity and enable ubiquitin chain restriction analysis

Sixteen ovarian tumor (OTU) family deubiquitinases (DUBs) exist in humans, and most members regulate cell-signaling cascades. Several OTU DUBs were reported to be ubiquitin (Ub) chain linkage specific, but comprehensive 
Sixteen ovarian tumor (OTU) family deubiquitinases (DUBs) exist in humans, and most members regulate cell-signaling cascades. Several OTU DUBs were reported to be ubiquitin (Ub) chain linkage specific, but comprehensive analyses are missing, and the underlying mechanisms of linkage specificity are unclear. Using Ub chains of all eight linkage types, we reveal that most human OTU enzymes are linkage specific, preferring one, two, or a defined subset of linkage types, including unstudied atypical Ub chains. Biochemical analysis and five crystal structures of OTU DUBs with or without Ub substrates reveal four mechanisms of linkage specificity. Additional Ub-binding domains, the ubiquitinated sequence in the substrate, and defined S1’ and S2 Ub-binding sites on the OTU domain enable OTU DUBs to distinguish linkage types. We introduce Ub chain restriction analysis, in which OTU DUBs are used as restriction enzymes to reveal linkage type and the relative abundance of Ub chains on substrates.
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Author:Tycho E. T. Mevissen, Manuela K. Hospenthal, Paul P. Geurink, Paul R. Elliott, Masato Akutsu, Nadia Arnaudo, Reggy Ekkebus, Yogesh Kulathu, Tobias Wauer, Farid El Oualid, Stefan M. V. Freund, Huib Ovaa, David Komander
URN:urn:nbn:de:hebis:30:3-316645
DOI:http://dx.doi.org/10.1016/j.cell.2013.05.046
ISSN:1097-4172
ISSN:0092-8674
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=23827681
Parent Title (English):Cell
Publisher:Elsevier
Place of publication:New York, NY
Document Type:Article
Language:English
Date of Publication (online):2013/07/03
Date of first Publication:2013/07/03
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2013/10/15
Volume:154
Pagenumber:30
First Page:169
Last Page:184
Note:
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
HeBIS PPN:362778051
Institutes:Biowissenschaften
Dewey Decimal Classification:570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
Sondersammelgebiets-Volltexte
Licence (German):License LogoCreative Commons - Namensnennung 3.0

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