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The inhibitors of apoptosis: there is more to life than Bcl2

Oncogene volume 22, pages 8568–8580 (2003)Cite this article

Abstract

The inhibitor of apoptosis (IAP) genes constitute a highly conserved family found in organisms as diverse as insects and mammals. These genes encode proteins that directly bind and inhibit caspases, and thus play a critical role in deciding cell fate. The IAPs are in turn regulated by endogenous proteins (second mitochondrial activator of caspases and Omi) that are released from the mitochondria during apoptosis. Overexpression of the IAPs, particularly the X-chromosome-linked IAP, has been shown to be protective in a variety of experimental animal models of human neurodegenerative diseases. Furthermore, overexpression of one or more of the IAPs in cancer cell lines and primary tumor samples appears to be a frequent event. IAP gene amplification and translocation events provide genetic evidence that further strengthens the case for classifying the IAPs as oncogenes. Therapeutic strategies that interfere with IAP expression or function are under investigation as an adjuvant to conventional chemotherapy- and radiation-based cancer therapy. This paper reviews the structure and function of the IAP family members and their inhibitors, and surveys the available evidence for IAP dysregulation in cancer.

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Acknowledgements

This work was supported by grants from the Canadian Institutes of Health Research (CIHR) (RGK and PL) and from the National Cancer Institute of Canada (RGK). RGK is a Howard Hughes Medical Institute International Research Scholar and CIHR Senior Scientist. PL is a CIHR New Investigator. We apologize to researchers whose papers were not cited due to space limitations. We thank all the members of the Korneluk and Liston laboratories for helpful discussions and advice.

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  1. Children's Hospital of Eastern Ontario, Research Institute, 401 Smyth Raod, Ottawa, K1H 8L1, Canada

    Peter Liston, Wai Gin Fong & Robert G Korneluk

  2. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, K1H 8M5, Canada

    Peter Liston & Robert G Korneluk

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Liston, P., Fong, W. & Korneluk, R. The inhibitors of apoptosis: there is more to life than Bcl2. Oncogene 22, 8568–8580 (2003). https://doi.org/10.1038/sj.onc.1207101

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