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The death effector domain protein family: regulators of cellular homeostasis

Nature Immunology volume 4, pages 404–409 (2003)Cite this article

Abstract

The death effector domain (DED) occurs in proteins that regulate programmed cell death. Both pro- and anti-apoptotic proteins containing DEDs have been identified. For Fas and possibly other death receptors, homotypic DED interactions connect the Fas-associated death domain (FADD) protein to caspase-8 and caspase-10 to mediate formation of the death-inducing signal complex. This complex can be inhibited by other DED-containing proteins. Accumulating evidence now suggests that DED-containing proteins have additional roles in controlling pathways of cellular activation and proliferation. Thus, the DED defines a family of proteins that may be pivotal to cellular homeostasis by establishing a 'cell renewal set point' that coregulates proliferation and apoptosis in parallel.

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Figure 1: Ribbon diagram of the hexahelical structure of the DED.
Figure 2: Sequence alignment of DED-containing human and viral proteins.
Figure 3: The functions and interacting roles of DED-containing proteins.

K.R.

Figure 4: Model of the control of the cell renewal set point.

C.C.

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Acknowledgements

We thank Y. Shi for assistance with Figure 1, and M. Ahmed, L. Yu and H. Su for critical reading of the manuscript, valuable discussion and sharing of unpublished data.

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  1. Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Michael D. Tibbetts, Lixin Zheng & Michael J. Lenardo

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Correspondence to Michael J. Lenardo.

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Tibbetts, M., Zheng, L. & Lenardo, M. The death effector domain protein family: regulators of cellular homeostasis. Nat Immunol 4, 404–409 (2003). https://doi.org/10.1038/ni0503-404

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