Road to Ruin: Targeting Proteins for Degradation in the Endoplasmic Reticulum

Overview

Journal Science

Specialty Science

Date 2011 Nov 26

PMID 22116878

Citations 343

Authors

Melanie H Smith

Hidde L Ploegh

Jonathan S Weissman

Affiliations

Soon will be listed here.

Abstract

Some nascent proteins that fold within the endoplasmic reticulum (ER) never reach their native state. Misfolded proteins are removed from the folding machinery, dislocated from the ER into the cytosol, and degraded in a series of pathways collectively referred to as ER-associated degradation (ERAD). Distinct ERAD pathways centered on different E3 ubiquitin ligases survey the range of potential substrates. We now know many of the components of the ERAD machinery and pathways used to detect substrates and target them for degradation. Much less is known about the features used to identify terminally misfolded conformations and the broader role of these pathways in regulating protein half-lives.

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