Guest Open Access Plus | Free Content | About | Sign in | New Users: Sign up | Mark List  

Current Molecular Medicine

Volume 6 Issue 1
ISSN: 1566-5240
eISSN: 1875-5666

 

   All Titles

  Divergent Roles of IRE1α and PERK in the Unfolded Protein Response
  pp.5-36 (32) Authors: Martin Schroder, Randal J. Kaufman
 
 
      Abstract

The endoplasmic reticulum (ER) provides unique machinery for the folding and posttranslational modification of many secretory and transmembrane proteins in eukaryotic cells. The unfolded protein response (UPR) is a signal transduction network from the ER to the nucleus activated when the folding demand imposed by nascent, unfolded polypeptide chains exceeds the capacity of the ER protein folding machinery. In all eukaryotes the UPR maintains the physiological balance between folding demand and capacity of the ER by regulating adaptive responses to this stress situation. These include an increase in the folding capacity of the ER through induction of ER resident molecular chaperones and protein foldases, and a decrease in the folding demand on the ER by upregulation of ER associated degradation (ERAD), attenuation of general translation in metazoans, and stimulation of ER synthesis to dilute the unfolded protein load. In higher eukaryotes the UPR gained control over inflammatory and immune responses by controlling the activity of the transcription factor NF-kB to combat viral infections associated with an increased synthesis of viral glycoproteins. Similarly, in multicellular organisms apoptotic programs are controlled by the UPR to eliminate cells whose folding problems in the ER cannot be resolved by coordinated regulation of adaptive, inflammatory, and immune responses. In this review we will summarize our current understanding of signal transduction mechanisms involved in the mammalian UPR, and discuss examples to highlight the regulation of adaptive, inflammatory, immune, and apoptotic responses by the UPR.

 
  Keywords: Endoplasmic reticulum, protein folding, molecular chaperones, signal transduction, conformational disease
  Affiliation: Howard Hughes Medical Institute, University of Michigan Medical Center, 4570 MSRBII, 1150 W. Medical Center Drive, Ann Arbor, MI 48109-0650, USA.
 
  Key: New Content Free Content Open Access Plus Subscribed Content

Bentham Science Publishers
www.benthamscience.com

 

  Copyright © 1994 - 2014   Bentham Science Publishers