The unfolded protein response at the crossroads of cellular life and death during endoplasmic reticulum stress
Jäger, Richard ; Bertrand, Mathieu J.M. ; Gorman, Adrienne M. ; Vandenabeele, Peter ; Samali, Afshin
Jäger, Richard
Bertrand, Mathieu J.M.
Gorman, Adrienne M.
Vandenabeele, Peter
Samali, Afshin
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Publication Date
2012-02-29
Type
Article
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Citation
Jäger, Richard; Bertrand, Mathieu J.M. Gorman, Adrienne M.; Vandenabeele, Peter; Samali, Afshin (2012). The unfolded protein response at the crossroads of cellular life and death during endoplasmic reticulum stress. Biology of the Cell 104 (5), 259-270
Abstract
One of the early cellular responses to endoplasmic reticulum (ER) stress is the activation of the unfolded protein response (UPR). ER stress and the UPR are both implicated in numerous human diseases and pathologies. In spite of this, our knowledge of the molecular mechanisms that regulate cell fate following ER stress is limited. The UPR is initiated by three ER transmembrane receptors: PKR-like ER kinase (PERK), activating transcription factor (ATF) 6 and inositol-requiring enzyme 1 (IRE1). These proteins sense the accumulation of unfolded proteins and their activation triggers specific adaptive responses to resolve the stress. Intriguingly, the very same receptors can initiate signalling pathways that lead to apoptosis when the attempts to resolve the ER stress fail. In this review, we describe the known pro-apoptotic signalling pathways emanating from activated PERK, ATF6 and IRE1 and discuss how their signalling switches from an adaptive to a pro-apoptotic response.
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Publisher
Wiley-Blackwell
Publisher DOI
10.1111/boc.201100055
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Attribution-NonCommercial-NoDerivs 3.0 Ireland