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Endoplasmic reticulum stress sensing in the unfolded protein response.

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 activation. BiP dissociation from Ire1 regulates this oligomeric equilibrium, ultimately modulating Ire1's sensitivity and duration of activation. The mechanistic principles of ER stress sensing are the focus of this review.

SUBMITTER: Gardner BM

PROVIDER: S-EPMC3578356 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Endoplasmic reticulum stress sensing in the unfolded protein response.

Gardner Brooke M BM Pincus David D Gotthardt Katja K Gallagher Ciara M CM Walter Peter P

Cold Spring Harbor perspectives in biology 20130301 3

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 ...[more]

PMID: 23388626

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Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR)

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