New Insights into the Physiological Role of Endoplasmic Reticulum-Associated Degradation. Issue 6 (June 2017)

• Record Type: Journal Article
• Authors: Qi, Ling; Tsai, Billy; Arvan, Peter
• Is Part Of: Trends in cell biology. Volume 27:Issue 6(2017)
• Page Start: 430
• Page End: 440
• Publication Date: 2017-06
• Subjects: Cytology -- Periodicals; Cytology -- Research -- Periodicals; 571.6
• DOI: 10.1016/j.tcb.2016.12.002
• Languages: English
• ISSNs: 0962-8924

Abstract

Abstract : Many human diseases are associated with mutations causing protein misfolding and aggregation in the endoplasmic reticulum (ER). ER-associated degradation (ERAD) is a principal quality-control mechanism responsible for targeting misfolded ER proteins for cytosolic degradation. However, despite years of effort, the physiological role of ERAD in vivo remains largely unknown. Several recent studies have reported intriguing phenotypes of mice deficient for ERAD function in specific cell types. These studies highlight that mammalian ERAD has been designed to perform a wide-range of cell-type-specific functions in vivo in a substrate-dependent manner. Trends: ERAD is the principal stress management mechanism used to clear both misfolded and normal proteins from the ER for cytosolic proteasomal degradation. The protein complex consisting of the E3 ligase Hrd1 and its cofactor Sel1L is the most conserved branch of ERAD. Sel1L–Hrd1 ERAD plays important roles in regulating ER homeostasis, metabolism, and immunity in a cell-type-specific manner. Several proteins including the UPR sensor IRE1α and pre-BCR have recently been identified as endogenous ERAD substrates.