Protein Partners of Deubiquitinating Enzymes

• Type of Material: Article
• Authors: Karen H. Ventii, Emory University; Keith D. Wilkinson, Emory University
• Language: English
• Date: 2008-09-01
• Publisher: Portland Press
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © The Authors Journal compilation © 2008 Biochemical Society
• Final Published Version (URL): http://www.biochemj.org/bj/414/bj4140161.htm
• Title of Journal or Parent Work: Biochemical Journal
• ISSN: 0264-6021
• Volume: 414
• Issue: 2
• Start Page: 161
• End Page: 175
• Grant/Funding Information: National Institute of General Medical Sciences : NIGMS
• Research Categories: Chemistry, Biochemistry

Abstract

Protein modification by ubiquitin and ubiquitin-like molecules is a critical regulatory process. Like most regulated protein modifications, ubiquitination is reversible. Deubiquitination, the reversal of ubiquitination, is quickly being recognized as an important regulatory strategy. Nearly a hundred human deubiquitinating enzymes (DUBs) in five different gene families oppose the action of several hundred ubiquitin ligases, suggesting that both ubiquitination and its reversal are highly regulated and specific processes. It has long been recognized that ubiquitin ligases are modular enzyme systems that often depend on scaffolds and adaptors to deliver substrates to the catalytically active macromolecular complex. While many DUBs bind ubiquitin with reasonable affinities (nM to μM) a larger number have little affinity but exhibit robust catalytic capability. Thus, it is apparent that these DUBs must acquire their substrates by binding the target protein in a conjugate or by associating with other macromolecular complexes. We would then expect that a study of protein partners of DUBs would reveal a variety of substrates, scaffolds, adapters and ubiquitin receptors. In this review we suggest that, like ligases, much of the regulation and specificity of deubiquitination arises from the association of DUBs with these protein partners.