The mechanism of OTUB1-mediated inhibition of ubiquitination.

ABSTRACT: Histones are ubiquitinated in response to DNA double-strand breaks (DSB), promoting recruitment of repair proteins to chromatin. UBC13 (also known as UBE2N) is a ubiquitin-conjugating enzyme (E2) that heterodimerizes with UEV1A (also known as UBE2V1) and synthesizes K63-linked polyubiquitin (K63Ub) chains at DSB sites in concert with the ubiquitin ligase (E3), RNF168 (ref. 3). K63Ub synthesis is regulated in a non-canonical manner by the deubiquitinating enzyme, OTUB1 (OTU domain-containing ubiquitin aldehyde-binding protein 1), which binds preferentially to the UBC13∼Ub thiolester. Residues amino-terminal to the OTU domain, which had been implicated in ubiquitin binding, are required for binding to UBC13∼Ub and inhibition of K63Ub synthesis. Here we describe structural and biochemical stu

SUBMITTER: Wiener R 

PROVIDER: S-EPMC3319311 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature