| Literature DB >> 26949185 |
Fabien Llambi1, Yue-Ming Wang2, Bernadette Victor3, Mao Yang3, Desiree M Schneider3, Sébastien Gingras3, Melissa J Parsons3, Janet H Zheng4, Scott A Brown3, Stéphane Pelletier3, Tudor Moldoveanu4, Taosheng Chen2, Douglas R Green5.
Abstract
The mitochondrial pathway of apoptosis is initiated by mitochondrial outer membrane permeabilization (MOMP). The BCL-2 family effectors BAX and BAK are thought to be absolutely required for this process. Here, we report that BCL-2 ovarian killer (BOK) is a bona fide yet unconventional effector of MOMP that can trigger apoptosis in the absence of both BAX and BAK. However, unlike the canonical effectors, BOK appears to be constitutively active and unresponsive to antagonistic effects of the antiapoptotic BCL-2 proteins. Rather, BOK is controlled at the level of protein stability by components of the endoplasmic reticulum (ER)-associated degradation pathway. BOK is ubiquitylated by the AMFR/gp78 E3 ubiquitin ligase complex and targeted for proteasomal degradation in a VCP/p97-dependent manner, which allows survival of the cell. When proteasome function, VCP, or gp78 activity is compromised, BOK is stabilized to induce MOMP and apoptosis independently of other BCL-2 proteins.Entities:
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Year: 2016 PMID： 26949185 PMCID： PMC5018360 DOI： 10.1016/j.cell.2016.02.026
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582