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Copyright © 2000 Cell Press. All rights reserved.
Molecular Cell, Volume 5, Issue 5, 897-904, 1 May 2000
doi:10.1016/S1097-2765(00)80330-5
Short Article
Perk Is Essential for Translational Regulation and Cell Survival during the Unfolded Protein Response
Heather P Harding1, Yuhong Zhang1, Anne Bertolotti1, Huiqing Zeng1 and David Ron1, *, *, 
Corresponding author: David Ron, 212 263 7786 (phone), 212 263 8951 (fax)Summary
Malfolded proteins in the endoplasmic reticulum (ER) inhibit translation initiation. This response is believed to be mediated by increased phosphorylation of eukaryotic initiation factor 2α (eIF2α) and is hypothesized to reduce the work load imposed on the folding machinery during stress. Here we report that mutating the gene encoding the ER stress–activated eIF2α kinase PERK abolishes the phosphorylation of eIF2α in response to accumulation of malfolded proteins in the ER resulting in abnormally elevated protein synthesis and higher levels of ER stress. Mutant cells are markedly impaired in their ability to survive ER stress and inhibition of protein 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.
