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ERADicate ER Stress or Die Trying

Abstract

Stress within the endoplasmic reticulum (ER) induces a sophisticated network of pathways termed the unfolded protein response (UPR), which is mediated through the ER transmembrane sensors PERK, ATF6, and IRE1. The UPR coordinates the temporary downregulation of protein translation, the upregulation of ER chaperones and folding machinery, and the enhanced expression of components necessary for ER-associated degradation (ERAD) essential for decreasing ER stress by clearing terminally misfolded proteins from the ER. Repetitive but futile folding attempts not only prolong ER stress but can also result in reactive oxygen species (ROS) generation, both of which may result in cell death. Additional mechanisms for decreasing stress and the protein load in the ER have been recently revealed. They include a newly identified function of IRE1 in degradation of select secretory protein mRNAs, a "preemptive" quality control responsible for averting translocation of select secretory proteins into the ER, upregulation of forward trafficking to allow misfolded proteins with intact exit signals to exit the ER, and upregulation of autophagy. The saturation or failure of some or all of these mechanisms can result in cell death and disease, including diabetes and a number of late-onset neurologic diseases.

Type Journal
ISBN 1523-0864 (Print)
Authors Kincaid, M. M.;Cooper, A. A. :
Garvan Authors A/Prof Antony Cooper
Publisher Name ANTIOXID REDOX SIGN
Published Date 2007-01-01 00:00:00
Published Volume 9
Published Issue 12
Published Pages 2373-87
URL http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17883326
Status Published In-print
OpenAccess Link https://publications.gimr.garvan.org.au/download.php?2225_11104/07 Kincaid ARS.pdf