@article{c894b8eb6ea64c48b384cb29c3f1d1a2,
title = "OTUB1 Co-opts Lys48-Linked Ubiquitin Recognition to Suppress E2 Enzyme Function",
abstract = "Ubiquitylation entails the concerted action of E1, E2, and E3 enzymes. We recently reported that OTUB1, a deubiquitylase, inhibits the DNA damage response independently of its isopeptidase activity. OTUB1 does so by blocking ubiquitin transfer by UBC13, the cognate E2 enzyme for RNF168. OTUB1 also inhibits E2s of the UBE2D and UBE2E families. Herewe elucidate the structural mechanism by which OTUB1 binds E2s to inhibit ubiquitin transfer. OTUB1 recognizes ubiquitin-charged E2s through contacts with both donor ubiquitin and the E2 enzyme. Surprisingly, free ubiquitin associates with the canonical distal ubiquitin-binding site on OTUB1 to promote formation of the inhibited E2 complex. Lys48 of donor ubiquitin lies near the OTUB1 catalytic site and the C terminus of free ubiquitin, a configuration that mimics the products of Lys48-linked ubiquitin chain cleavage. OTUB1 therefore co-opts Lys48-linked ubiquitin chain recognition to suppress ubiquitin conjugation and the DNA damage response.",
author = "Juang, {Yu Chi} and Landry, {Marie Claude} and Mario Sanches and Vinayak Vittal and Leung, {Charles C.Y.} and Ceccarelli, {Derek F.} and Mateo, {Abigail Rachele F.} and Pruneda, {Jonathan N.} and Mao, {Daniel Y.L.} and Szilard, {Rachel K.} and Stephen Orlicky and Meagan Munro and Brzovic, {Peter S.} and Klevit, {Rachel E.} and Frank Sicheri and Daniel Durocher",
note = "Funding Information: The order of M.-C.L. and Y.-C.J. in the author list was determined by sortition. We thank staff at the Canadian Light Source and I. Kourinov and staff at Argonne National Laboratory at the Advanced Photon Source on the Northeastern Collaborative Access Team beamlines for assistance with diffraction experiments. M.-C.L. holds a postdoctoral Fellowship of the Canadian Breast Cancer Foundation. F.S. is a Canada Research Chair (Tier 1) in Structural Principles of Signal Transduction, and D.D. is the Thomas Kierans Chair in Mechanisms of Cancer Development and a Canada Research Chair (Tier 1) in Molecular Genetics of the DNA Damage Response. This work was supported by Canadian Institutes of Health Research (CIHR) grants MOP84297 to D.D. and MOP57795 to F.S., and by National Institutes of Health (NIH) grant R01 GM088055 to R.E.K. ",
year = "2012",
month = feb,
day = "10",
doi = "10.1016/j.molcel.2012.01.011",
language = "English (US)",
volume = "45",
pages = "384--397",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "3",
}