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The unfolded protein response at the crossroads of cellular life and death during endoplasmic reticulum stress

  • 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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Document Type:Article
Author:Richard Jäger, Mathieu J. M. Bertrand, Adrienne M. Gorman, Peter Vandenabeele, Afshin Samali
Parent Title (English):Biol Cell. (Biology of the Cell)
First Page:259
Last Page:270
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=22268789
Date of first publication:2012/01/23
Departments, institutes and facilities:Institut für funktionale Gen-Analytik (IFGA)
Dewey Decimal Classification (DDC):6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Entry in this database:2018/07/14