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The unfolded protein response at the crossroads of cellular life and death during endoplasmic reticulum stress
Author(s) -
Jäger Richard,
Bertrand Mathieu J.M.,
Gorman Adrienne M.,
Vandenabeele Peter,
Samali Afshin
Publication year - 2012
Publication title -
biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 85
eISSN - 1768-322X
pISSN - 0248-4900
DOI - 10.1111/boc.201100055
Subject(s) - unfolded protein response , endoplasmic reticulum , atf6 , microbiology and biotechnology , biology , eif 2 kinase , signal transduction , transcription factor , transmembrane protein , activating transcription factor , receptor , kinase , protein kinase a , biochemistry , gene , cyclin dependent kinase 2
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.