Title: Pro-apoptotic signaling induced by photo-oxidative ER stress is amplified by Noxa, not Bim
Authors: Verfaillie, Tom *
van Vliet, Alex *
GARG, Abhishek
Dewaele, Michael
Rubio, Noemi
Gupta, Sanjeev
de Witte, Peter
Samali, Afshin
Agostinis, Patrizia # ×
Issue Date: Aug-2013
Publisher: Academic Press
Series Title: Biochemical and Biophysical Research Communications vol:438 issue:3 pages:500-6
Article number: 10.1016/j.bbrc.2013.07.107
Abstract: Pro-apoptotic signaling instigated by endoplasmic reticulum (ER) stress is tightly governed by the BH3-only proteins like Noxa and Bim, which help trigger apoptosis, in part by inactivating mitochondria protecting proteins like Mcl-1. Bim/Noxa-based pro-apoptotic signaling has been implicated for various ER stressors but not yet for those causing "ER-focused" production of severe oxidative stress. In the present study we found that photo-oxidative (phox)-ER stress induced by hypericin-based photodynamic therapy is associated with activation of PERK (an ER sessile, stress sensor), robust induction of CHOP (a pro-apoptotic transcription factor) and induction of Bim and Noxa (accompanied by an eventual drop in Mcl-1 levels). Interestingly Noxa, but not Bim, contributed toward phox-ER stress induced apoptosis, regulated by PERK in a CHOP-independent, temporally-defined manner. These observations shed further light on complex signaling pathways elicited byphox-ER stress and vouch for directing more investigation toward the role of PERK in cell death governance.
ISSN: 0006-291X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Cell Death Research & Therapy
* (joint) first author
× corresponding author
# (joint) last author

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