Perk is essential for translational regulation and cell survival during the unfolded protein response

Citation
Hp. Harding et al., Perk is essential for translational regulation and cell survival during the unfolded protein response, MOL CELL, 5(5), 2000, pp. 897-904
Citations number
24
Categorie Soggetti
Cell & Developmental Biology
Journal title
MOLECULAR CELL
ISSN journal
10972765 → ACNP
Volume
5
Issue
5
Year of publication
2000
Pages
897 - 904
Database
ISI
SICI code
1097-2765(200005)5:5<897:PIEFTR>2.0.ZU;2-8
Abstract
Malfolded proteins in the endoplasmic reticulum (ER) inhibit translation in itiation. This response is believed to be mediated by increased phosphoryla tion of eukaryotic initiation factor 2 alpha (eIF2 alpha) and is hypothesiz ed to reduce the work load imposed on the folding machinery during stress. Here we report that mutating the gene encoding the ER stress-activated eIF2 alpha kinase PERK abolishes the phosphorylation of eIF2 alpha in response to accumulation of malfolded proteins in the ER resulting in abnormally ele vated protein synthesis and higher levels of ER stress. Mutant cells are ma rkedly impaired in their ability to survive ER stress and inhibition of pro tein synthesis by cycloheximide treatment during ER stress ameliorates this impairment. PERK thus plays a major role in the ability of cells to adapt to ER stress.