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FLIP and the death effector domain family

Oncogene volume 27, pages 6216–6227 (2008)Cite this article

Abstract

Death effector domains (DEDs) are protein interaction modules found in a number of proteins known to regulate apoptosis from death receptors. The core DED family members that orchestrate programmed cell death from death receptors include the adaptor protein FADD, the initiator caspases procaspases-8 and -10 and the regulatory protein c-FLIP. Through homotypic DED interactions, these proteins assemble into the death-inducing signaling complex (DISC) to regulate initiator caspase activation and launch the apoptotic proteolytic cascade. A considerable body of evidence, however, is revealing that the same core group of DED-containing proteins also paradoxically promotes survival and proliferation in lymphocytes and possibly other cell types. This review delves into recent findings regarding these two opposing functional aspects of the core DED proteins. We discuss the current effort expanding our structural and biochemical view of how DED proteins assemble into the DISC to fully activate initiator caspases and execute cell death, and finally we examine details linking the same proteins to proliferation and describe how this outcome might be achieved through restricted activation of initiator caspases.

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Acknowledgements

Work from Yigong Shi's laboratory in this area of research was supported by a grant from the National Institutes of Health (2 R01 CA90269). Jong W Yu is a Damon Runyon Fellow supported by the Damon Runyon Cancer Research Foundation (DRG-1905-06).

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  1. Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ, USA

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Yu, J., Shi, Y. FLIP and the death effector domain family. Oncogene 27, 6216–6227 (2008). https://doi.org/10.1038/onc.2008.299

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  • DOI: https://doi.org/10.1038/onc.2008.299

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