BOK Is a Non-canonical BCL-2 Family Effector of Apoptosis Regulated by ER-Associated Degradation

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2016 Mar 8

PMID 26949185

Citations 137

Authors

Fabien Llambi

Yue-Ming Wang

Bernadette Victor

Mao Yang

Desiree M Schneider

Sebastien Gingras

Melissa J Parsons

Janet H Zheng

Scott A Brown

Stephane Pelletier

Tudor Moldoveanu

Taosheng Chen

Douglas R Green

Affiliations

Soon will be listed here.

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.

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