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The Bcl-2 family: roles in cell survival and oncogenesis

Abstract

Apoptosis, the cell-suicide programme executed by caspases, is critical for maintaining tissue homeostasis, and impaired apoptosis is now recognized to be a key step in tumorigenesis. Whether a cell should live or die is largely determined by the Bcl-2 family of anti- and proapoptotic regulators. These proteins respond to cues from various forms of intracellular stress, such as DNA damage or cytokine deprivation, and interact with opposing family members to determine whether or not the caspase proteolytic cascade should be unleashed. This review summarizes current views of how these proteins sense stress, interact with their relatives, perturb organelles such as the mitochondrion and endoplasmic reticulum and govern pathways to caspase activation. It briefly explores how family members influence cell-cycle entry and outlines the evidence for their involvement in tumour development, both as oncoproteins and tumour suppressors. Finally, it discusses the promise of novel anticancer therapeutics that target these vital regulators.

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Acknowledgements

We warmly thank our colleagues, particularly A Strasser, A Harris, H Puthalakath, P Bouillet, C Day, M Hinds, J Baell, P Colman, K Watson, A Roberts and A Wei for many discussions that influenced this review; G Filby for editorial assistance and P Maltezos for figure preparation. This work was supported in part by grants from the National Health and Research Council of Australia (ID No 257502), the US National Institutes of Health (CA43540 and CA80188) and the Leukaemia and Lymphoma Society (SCOR grant). DCSH is a Viertel Fellow.

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Cory, S., Huang, D. & Adams, J. The Bcl-2 family: roles in cell survival and oncogenesis. Oncogene 22, 8590–8607 (2003). https://doi.org/10.1038/sj.onc.1207102

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