Next Article in Journal / Special Issue
Bacterial Effectors and Their Functions in the Ubiquitin-Proteasome System: Insight from the Modes of Substrate Recognition
Previous Article in Journal
microRNAs and Cardiac Cell Fate
Previous Article in Special Issue
Ubiquitin Signaling: Extreme Conservation as a Source of Diversity
Article Menu

Export Article

Open AccessReview
Cells 2014, 3(3), 824-847; doi:10.3390/cells3030824

Regulation of Endoplasmic Reticulum-Associated Protein Degradation (ERAD) by Ubiquitin

Department of Genetics, University of Seville, Av. Reina Mercedes 6, 41012 Seville, Spain
*
Author to whom correspondence should be addressed.
Received: 6 June 2014 / Revised: 9 July 2014 / Accepted: 20 July 2014 / Published: 5 August 2014
(This article belongs to the Special Issue Protein Ubiquitination)
View Full-Text   |   Download PDF [1284 KB, uploaded 5 August 2014]   |  

Abstract

Quality control of protein folding inside the endoplasmic reticulum (ER) includes chaperone-mediated assistance in folding and the selective targeting of terminally misfolded species to a pathway called ER-associated protein degradation, or simply ERAD. Once selected for ERAD, substrates will be transported (back) into the cytosol, a step called retrotranslocation. Although still ill defined, retrotranslocation likely involves a protein conducting channel that is in part formed by specific membrane-embedded E3 ubiquitin ligases. Early during retrotranslocation, reversible self-ubiquitination of these ligases is thought to aid in initiation of substrate transfer across the membrane. Once being at least partially exposed to the cytosol, substrates will become ubiquitinated on the cytosolic side of the ER membrane by the same E3 ubiquitin ligases. Ubiquitin on substrates was originally thought to be a permanent modification that (1) promotes late steps of retrotranslocation by recruiting the energy-providing ATPase Cdc48p/p97 via binding to its associated adaptor proteins and that (2) serves to target substrates to the proteasome. Recently it became evident, however, that the poly-ubiquitin chains (PUCs) on ERAD substrates are often subject to extensive remodeling, or processing, at several stages during ERAD. This review recapitulates the current knowledge and recent findings about PUC processing on ERAD substrates and ubiquitination of ERAD machinery components and discusses their functional consequences. View Full-Text
Keywords: ubiquitin; ERAD; Cdc48; p97; proteasome; E3 ubiquitin ligase; deubiquitinase ubiquitin; ERAD; Cdc48; p97; proteasome; E3 ubiquitin ligase; deubiquitinase
Figures

This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Lemus, L.; Goder, V. Regulation of Endoplasmic Reticulum-Associated Protein Degradation (ERAD) by Ubiquitin. Cells 2014, 3, 824-847.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Cells EISSN 2073-4409 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top