The unfolded protein response: integrating stress signals through the stress sensor IRE1α.

Abstract:

:Stress induced by accumulation of unfolded proteins at the endoplasmic reticulum (ER) is a classic feature of secretory cells and is observed in many tissues in human diseases including cancer, diabetes, obesity, and neurodegeneration. Cellular adaptation to ER stress is achieved by the activation of the unfolded protein response (UPR), an integrated signal transduction pathway that transmits information about the protein folding status at the ER to the nucleus and cytosol to restore ER homeostasis. Inositol-requiring transmembrane kinase/endonuclease-1 (IRE1α), the most conserved UPR stress sensor, functions as an endoribonuclease that processes the mRNA of the transcription factor X-box binding protein-1 (XBP1). IRE1α signaling is a highly regulated process, controlled by the formation of a dynamic scaffold onto which many regulatory components assemble, here referred to as the UPRosome. Here we provide an overview of the signaling and regulatory mechanisms underlying IRE1α function and discuss the emerging role of the UPR in adaptation to protein folding stress in specialized secretory cells and in pathological conditions associated with alterations in ER homeostasis.

journal_name

Physiol Rev

journal_title

Physiological reviews

authors

Hetz C,Martinon F,Rodriguez D,Glimcher LH

doi

10.1152/physrev.00001.2011

subject

Has Abstract

pub_date

2011-10-01 00:00:00

pages

1219-43

issue

4

eissn

0031-9333

issn

1522-1210

pii

91/4/1219

journal_volume

91

pub_type

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