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Inhibitor of apoptosis proteins in Drosophila: gatekeepers of death

  • Apoptosis in Drosophila
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Abstract

Regulation of apoptosis is crucial to ensure cellular viability, and failure to do so is linked to several human pathologies. The apoptotic cell death programme culminates in the activation of caspases, a family of highly specific cysteine proteases essential for the destruction of the cell. Although best known for their role in executing apoptosis, caspases also play important signalling roles in non-apoptotic processes, such as regulation of actin dynamics, innate immunity, cell proliferation, differentiation and survival. Under such conditions, caspases are activated without killing the cell. Caspase activation and activity is subject to complex regulation, and various cellular and viral inhibitors have been identified that control the activity of caspases in their apoptotic and non-apoptotic roles. Members of the Inhibitor of APoptosis (IAP) protein family ensure cell viability in Drosophila by directly binding to caspases and regulating their activities in a ubiquitin-dependent manner. The observation that IAPs are essential for cell survival in Drosophila, and are frequently deregulated in human cancer, contributing to tumourigenesis, chemoresistance, disease progression and poor patient survival, highlights the importance of this family of caspase regulators in health and disease. Here we summarise recent advances from Drosophila that start to elucidate how the cellular response to caspase activation is modulated by IAPs and their regulators.

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Acknowledgments

We would like to apologise to our colleagues for omitting many relevant publications due to space limitation. We are grateful to Meike Broemer for critical reading of the manuscript and helpful comments, and we would like to thank Marketa Zvelebil for help with structural modelling. This work was supported by Breakthrough Breast Cancer and Association for International Cancer Research (AICR). We acknowledge NHS funding to the NIHR Biomedical Research Centre.

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  1. The Breakthrough Toby Robins Breast Cancer Research Centre, Mary-Jean Mitchell Green Building, Chester Beatty Laboratories, Institute of Cancer Research, Fulham Road, London, SW3 6JB, UK

    Mariam Orme & Pascal Meier

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Correspondence to Mariam Orme or Pascal Meier.

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Orme, M., Meier, P. Inhibitor of apoptosis proteins in Drosophila: gatekeepers of death. Apoptosis 14, 950–960 (2009). https://doi.org/10.1007/s10495-009-0358-2

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