title: Death effecter domain for the assembly of death-inducing signaling complex.
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.
authors.affiliation: Department of Chemistry, School of Natural Sciences, Soongsil University, Seoul, 156-743, Korea, jinkukyang@ssu.ac.kr.
authors.forename: Jin Kuk
authors.initials: JK
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis; D053418:Death Domain Receptor Signaling Adaptor Proteins / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D015398:Signal Transduction
chemical_list: D053418:Death Domain Receptor Signaling Adaptor Proteins