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Death effecter domain for the assembly of death-inducing signaling complex

  • The Domains of Apoptosis and Inflammation
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Abstract

Death-inducing signaling complex (DISC) is a platform for the activation of initiator caspase in extrinsic apoptosis. Assembly of DISC is accomplished by two different types of homotypic interaction: one is between death domains (DDs) of a death receptor and FADD, and the other is between death effecter domains (DEDs) of FADD, procaspase-8/-10 and cFLIP. Recent biochemical investigations on the stoichiometry of DISC have revealed that single-DED-containing FADD exists in DISC in a substantially lower abundance than the sum of tandem-DEDs-containing components that are procaspase-8 and cFLIP. In addition, the homology models of the tandem DEDs in procaspase-8 and cFLIP show that two different interaction faces, H1–H4 face and H2–H5 face, are exposed for possible inter-molecular DED–DED interactions. These recent findings led to a proposal of the DED chain model for the interactions between FADD, procaspase-8 and cFLIP in DISC. This emerging view provides new insights on the topology of DED–DED network in DISC and furthermore on how procaspase-8 and cFLIP cluster for dimerization and proteolytic activation.

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Acknowledgments

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF-2014R1A2A2A01006834).

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  1. Department of Chemistry, School of Natural Sciences, Soongsil University, Seoul, 156-743, Korea

    Jin Kuk Yang

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  1. Jin Kuk Yang
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Correspondence to Jin Kuk Yang.

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Yang, J.K. Death effecter domain for the assembly of death-inducing signaling complex. Apoptosis 20, 235–239 (2015). https://doi.org/10.1007/s10495-014-1060-6

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  • DOI: https://doi.org/10.1007/s10495-014-1060-6

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