Ubiquitin Chain-elongating Enzyme UBE2S Activates the RING E3 Ligase APC/C for Substrate Priming

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2020 May 13

PMID 32393902

Citations 23

Authors

Raquel C Martinez-Chacin

Tatyana Bodrug

Derek L Bolhuis

Katarzyna M Kedziora

Thomas Bonacci

Alban Ordureau

Morgan E Gibbs

Florian Weissmann

Renping Qiao

Gavin D Grant

Jeanette G Cook

Jan-Michael Peters

J Wade Harper

Michael J Emanuele

Nicholas G Brown

Affiliations

Soon will be listed here.

Abstract

The interplay between E2 and E3 enzymes regulates the polyubiquitination of substrates in eukaryotes. Among the several RING-domain E3 ligases in humans, many utilize two distinct E2s for polyubiquitination. For example, the cell cycle regulatory E3, human anaphase-promoting complex/cyclosome (APC/C), relies on UBE2C to prime substrates with ubiquitin (Ub) and on UBE2S to extend polyubiquitin chains. However, the potential coordination between these steps in ubiquitin chain formation remains undefined. While numerous studies have unveiled how RING E3s stimulate individual E2s for Ub transfer, here we change perspective to describe a case where the chain-elongating E2 UBE2S feeds back and directly stimulates the E3 APC/C to promote substrate priming and subsequent multiubiquitination by UBE2C. Our work reveals an unexpected model for the mechanisms of RING E3-dependent ubiquitination and for the diverse and complex interrelationship between components of the ubiquitination cascade.

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