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BH3-only proteins and their roles in programmed cell death

Oncogene volume 27, pages S128–S136 (2008)Cite this article

Abstract

The Bcl-2 family of proteins controls the mitochondrial pathway to apoptosis. It consists of pro-survival and pro-apoptotic members, and their interactions decide whether apoptogenic factor confined to the mitochondrial intermembrane space can leak to the cytosol. Despite the intense efforts to understand the molecular mechanisms that lead to the permeabilization of the mitochondrial membrane, this particular issue remains a matter of intense controversy. It is well accepted that pro-apoptotic Bax and Bak are directly responsible for the damage to the mitochondria, but pro-survival family members prevent them from doing so. It is also accepted that stress signals activate selected Bcl-2 homology (BH)3-only proteins. But do these BH3-only proteins bind and activate Bax and Bak directly, or do they inhibit the pro-survival family members?

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Acknowledgements

This work was supported by the NHMRC (Program Grant, Fellowship, Career Development Award and Project Grant) and the Charles and Sylvia Viertel Charitable Foundation. We are grateful to our colleagues at WEHI for stimulating discussions and insightful comments. We apologize to the authors whose contributions have not been cited owing to space limitations.

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  1. The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

    M Giam, D C S Huang & P Bouillet

  2. Department of Medical Biology, The University of Melbourne, Melbourne, Australia

    M Giam

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Correspondence to P Bouillet.

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Giam, M., Huang, D. & Bouillet, P. BH3-only proteins and their roles in programmed cell death. Oncogene 27 (Suppl 1), S128–S136 (2008). https://doi.org/10.1038/onc.2009.50

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