reviewCold Spring Harbor Perspectives in BiologyFeb 6, 2013BRONZE OA

Endoplasmic Reticulum Stress Sensing in the Unfolded Protein Response

University of California, San Francisco · Howard Hughes Medical Institute

PubMed
Indexed incrossrefpubmed

Abstract

Secretory and transmembrane proteins enter the endoplasmic reticulum (ER) as unfolded proteins and exit as either folded proteins in transit to their target organelles or as misfolded proteins targeted for degradation. The unfolded protein response (UPR) maintains the protein-folding homeostasis within the ER, ensuring that the protein-folding capacity of the ER meets the load of client proteins. Activation of the UPR depends on three ER stress sensor proteins, Ire1, PERK, and ATF6. Although the consequences of activation are well understood, how these sensors detect ER stress remains unclear. Recent evidence suggests that yeast Ire1 directly binds to unfolded proteins, which induces its oligomerization and…

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