BID, BIM, and PUMA Are Essential for Activation of the BAX- and BAK-dependent Cell Death Program

Overview

Journal Science

Specialty Science

Date 2010 Dec 4

PMID 21127253

Citations 269

Authors

Decheng Ren

Ho-Chou Tu

Hyungjin Kim

Gary X Wang

Gregory R Bean

Osamu Takeuchi

John R Jeffers

Gerard P Zambetti

James J-D Hsieh

Emily H-Y Cheng

Affiliations

Soon will be listed here.

Abstract

Although the proteins BAX and BAK are required for initiation of apoptosis at the mitochondria, how BAX and BAK are activated remains unsettled. We provide in vivo evidence demonstrating an essential role of the proteins BID, BIM, and PUMA in activating BAX and BAK. Bid, Bim, and Puma triple-knockout mice showed the same developmental defects that are associated with deficiency of Bax and Bak, including persistent interdigital webs and imperforate vaginas. Genetic deletion of Bid, Bim, and Puma prevented the homo-oligomerization of BAX and BAK, and thereby cytochrome c-mediated activation of caspases in response to diverse death signals in neurons and T lymphocytes, despite the presence of other BH3-only molecules. Thus, many forms of apoptosis require direct activation of BAX and BAK at the mitochondria by a member of the BID, BIM, or PUMA family of proteins.

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