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Biochim Biophys Acta. 2011 Apr;1813(4):508-20. doi: 10.1016/j.bbamcr.2010.11.024. Epub 2010 Dec 10.

BH3-only proteins: Orchestrators of apoptosis.

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  • 1Department of Biochemistry and Biomedical Sciences and McMaster University, Hamilton, Ontario, Canada.

Abstract

The BH3-only proteins of Bcl-2 family are essential initiators of apoptosis that propagate extrinsic and intrinsic cell death signals. The interaction of BH3-only proteins with other Bcl-2 family members is critical for understanding the core machinery that controls commitment to apoptosis by permeabilizing the mitochondrial outer membrane. BH3-only proteins promote apoptosis by both directly activating Bax and Bak and by suppressing the anti-apoptotic proteins at the mitochondria and the endoplasmic reticulum. To prevent constitutive cell death, BH3-only proteins are regulated by a variety of mechanisms including transcription and post-translational modifications that govern specific protein-protein interactions. Furthermore, BH3-only proteins also control the initiation of autophagy, another important pathway regulating cell survival and death. Emerging evidence indicates that the interaction of BH3-only proteins with membranes regulates binding to other Bcl-2 family members, thereby specifying function. Due to the important role of BH3-only proteins in the regulation of cell death, several promising BH3-mimetic drugs that are active in pre-clinical models are currently being tested as anti-cancer agents. This article is part of a Special Issue entitled Mitochondria: the deadly organelle.

Copyright © 2010 Elsevier B.V. All rights reserved.

PMID:
21146563
[PubMed - indexed for MEDLINE]
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