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Current Protein & Peptide Science

Editor-in-Chief

ISSN (Print): 1389-2037
ISSN (Online): 1875-5550

Roles of p97-Associated Deubiquitinases in Protein Quality Control at the Endoplasmic Reticulum

Author(s): Yanfen Liu and Yihong Ye

Volume 13, Issue 5, 2012

Page: [436 - 446] Pages: 11

DOI: 10.2174/138920312802430608

Price: $65

Abstract

To maintain protein homeostasis in the ER, an ER protein quality control system retains unfolded polypeptides and misassembled membrane proteins, allowing only properly folded proteins to exit the ER. Misfolded proteins held in the ER are retrotranslocated into the cytosol, ubiquitinated, and degraded by the proteasome through the ER-associated degradation pathway (ERAD). By timely eliminating misfolded proteins, the ERAD system alleviates cytotoxic stress imposed by protein misfolding. It is well established that ER-associated ubiquitin ligases play pivotal roles in ERAD by assembling ubiquitin conjugates on retrotranslocation substrates, which serve as degradation signals for the proteasome. Surprisingly, recent studies have revealed an equally important function for deubiquitinases (DUBs), enzymes that disassemble ubiquitin chains, in ERAD. Intriguingly, many ERAD specific DUBs are physically associated with the retrotranslocation- driving ATPase p97. Here we discuss the potential functions of p97-associated DUBs including ataxin-3 and YOD1. Our goal is to integrate the emerging evidence into models that may explain how protein quality control could benefit from deubiquitination, a process previously deemed destructive for proteasomal degradation.

Keywords: p97/VCP/Cdc48, ERAD/retrotranslocation, deubiquitination, ataxin-3, YOD1, proteasome, ubiquitin, ER protein quality control


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