| Literature DB >> 25306923 |
Nicholas G Brown1, Edmond R Watson2, Florian Weissmann3, Marc A Jarvis3, Ryan VanderLinden4, Christy R R Grace1, Jeremiah J Frye1, Renping Qiao3, Prakash Dube5, Georg Petzold3, Shein Ei Cho1, Omar Alsharif1, Ju Bao1, Iain F Davidson3, Jie J Zheng1, Amanda Nourse1, Igor Kurinov6, Jan-Michael Peters7, Holger Stark8, Brenda A Schulman9.
Abstract
Polyubiquitination by E2 and E3 enzymes is a predominant mechanism regulating protein function. Some RING E3s, including anaphase-promoting complex/cyclosome (APC), catalyze polyubiquitination by sequential reactions with two different E2s. An initiating E2 ligates ubiquitin to an E3-bound substrate. Another E2 grows a polyubiquitin chain on the ubiquitin-primed substrate through poorly defined mechanisms. Here we show that human APC's RING domain is repurposed for dual functions in polyubiquitination. The canonical RING surface activates an initiating E2-ubiquitin intermediate for substrate modification. However, APC engages and activates its specialized ubiquitin chain-elongating E2 UBE2S in ways that differ from current paradigms. During chain assembly, a distinct APC11 RING surface helps deliver a substrate-linked ubiquitin to accept another ubiquitin from UBE2S. Our data define mechanisms of APC/UBE2S-mediated polyubiquitination, reveal diverse functions of RING E3s and E2s, and provide a framework for understanding distinctive RING E3 features specifying ubiquitin chain elongation.Entities:
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Year: 2014 PMID： 25306923 PMCID： PMC4272865 DOI： 10.1016/j.molcel.2014.09.009
Source DB: PubMed Journal: Mol Cell ISSN： 1097-2765 Impact factor: 17.970