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Updated: Jan 4, 2026

Examining BCL-2 Family Function with Large Unilamellar Vesicles
Published on: October 5, 2012
Targeting BAX ubiquitin-binding sites reveals that BAX activation is essential for its ubiquitin-dependent
Rui Peng1, Jialin Zhu1, Shujin Deng1
1College of Life Sciences, Sichuan University, Chengdu, Sichuan, China.
Abstract:
BAX is an important proapoptotic protein of the BCL-2 family, and its stability is essential for the regulation of the mitochondrial apoptotic pathway. A previous study revealed that BAX could undergo degradation through the ubiquitin-proteasome pathway. In this study, we identified two lysine sites, K21 and K123, that were critical ubiquitin-binding sites in BAX. Mutation of these two sites prolonged the half-life of BAX and also affected its proapoptotic ability. Intriguingly, we found that ABT-737, a BCL-2 inhibitor, significantly enhanced TRAIL-induced BAX degradation in HCT116 cells and increased TRAIL-induced apoptosis in the HCT116 only with the BAX K21R/K123R mutant, not other BAX mutants. In addition, overexpression of PARKIN, an E3 ubiquitin ligase targeting BAX, dramatically decreased BAX protein level when only treated with ABT-737 in HCT116 cells. Therefore, we speculated that BAX activation is essential for its ubiquitin-dependent degradation.
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