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Updated: May 9, 2026

Examining BCL-2 Family Function with Large Unilamellar Vesicles
Published on: October 5, 2012
Pro-apoptotic signaling induced by photo-oxidative ER stress is amplified by Noxa, not Bim
Tom Verfaillie1, Alexander van Vliet, Abhishek D Garg
1Laboratory of Cell Death Research and Therapy, Department of Cellular and Molecular Medicine, KU Leuven, Belgium.
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.
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