Protein quality control in the ER: balancing the ubiquitin checkbook

• Published in: Trends in cell biology Vol. 22; no. 1; pp. 22 - 32
• Main Authors: Claessen, Jasper H.L., Kundrat, Lenka, Ploegh, Hidde L.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.01.2012
• Subjects: Animals; endoplasmic reticulum; Endoplasmic Reticulum - metabolism; Humans; Pathology; polypeptides; proteasome endopeptidase complex; Protein Binding; Protein Folding; Protein Processing, Post-Translational; proteolysis; quality control; Substrate Specificity; ubiquitin; Ubiquitin - metabolism; ubiquitin-protein ligase
• ISSN: 0962-8924; 1879-3088; 1879-3088
• DOI: 10.1016/j.tcb.2011.09.010

Protein maturation in the endoplasmic reticulum (ER) is subject to stringent quality control. Terminally misfolded polypeptides are usually ejected into the cytoplasm and targeted for destruction by the proteasome. Ubiquitin conjugation is essential for both extraction and proteolysis. We discuss the role of the ubiquitin conjugation machinery in this pathway and focus on the role of ubiquitin ligase complexes as gatekeepers for membrane passage. We then examine the type of ubiquitin modification applied to the misfolded ER protein and the role of de-ubiquitylating enzymes in the extraction of proteins from the ER.