BCL-2 modulates the unfolded protein response by enhancing splicing of X-box binding protein-1

Biochemical and Biophysical Research Communications
Triona Ni ChonghaileAfshin Samali

Abstract

Accumulation of unfolded proteins within the endoplasmic reticulum (ER) triggers a highly conserved stress response mechanism termed the unfolded protein response (UPR). The UPR is a complex series of signaling pathways controlled by ER localized transmembrane receptors, PERK, ATF6 and IRE1α. Following activation IRE1α splices XBP-1 mRNA facilitating the formation of a potent transcription factor, spliced XBP-1. The BCL-2 family members, BAX and BAK, in addition to the mitochondrion also localize to the ER and have been demonstrated to directly interact with IRE1α promoting its activity. In this study we show that in addition to BAX and BAK, the anti-apoptotic BCL-2 protein can regulate IRE1α activity. Enhanced splicing of XBP-1 was observed in BCL-2 overexpressing cells implicating BCL-2 in the complex regulation of IRE1α activity.

References

Aug 12, 2004·Molecular Cell·Han-Jung ChaeJohn C Reed
Dec 23, 2004·Proceedings of the National Academy of Sciences of the United States of America·Scott A OakesStanley J Korsmeyer
Feb 16, 2006·Proceedings of the National Academy of Sciences of the United States of America·Béatrice Bailly-MaitreJohn C Reed
May 27, 2006·Cell Death and Differentiation·P Pinton, R Rizzuto
Sep 6, 2006·EMBO Reports·Eva SzegezdiAfshin Samali
Jul 3, 2007·Cell·Hamsa PuthalakathAndreas Strasser
Dec 22, 2007·Nature Reviews. Molecular Cell Biology·Richard J Youle, Andreas Strasser

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Citations

Jun 18, 2017·Cell Death and Differentiation·Philippe PihánClaudio Hetz
Feb 25, 2017·Cell Death and Differentiation·Atan Gross, Samuel G Katz

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