Key role for Bak activation and Bak-Bax interaction in the apoptotic response to vinblastine.

ABSTRACT: Microtubule inhibitors such as vinblastine cause mitotic arrest and subsequent apoptosis through the intrinsic mitochondrial pathway. However, although Bcl-2 family proteins have been implicated as distal mediators, their precise role is largely unknown. In this study, we investigated the role of Bak in vinblastine-induced apoptosis. Bak was mainly monomeric in untreated KB-3 cells, and multimers corresponding to dimer, trimer, and higher oligomers were observed after vinblastine treatment. The oligomeric Bak species were strongly diminished in cells stably overexpressing Bcl-xL. Immunoprecipitation with a conformation-dependent Bak antibody revealed that vinblastine induced Bak activation. Reciprocal immunoprecipitations indicated that vinblastine induced the interaction of active Bak wit

SUBMITTER: Upreti M 

PROVIDER: S-EPMC3276366 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature