Homotypic FADD interactions through a conserved RXDLL motif are required for death receptor-induced apoptosis
- Authors
- Muppidi, J. R.; Lobito, A. A.; Ramaswamy, M.; Yang, J. K.; Wang, L.; Wu, H.; Siegel, R. M.
- Issue Date
- Oct-2006
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- CELL DEATH AND DIFFERENTIATION, v.13, no.10, pp.1641 - 1650
- Journal Title
- CELL DEATH AND DIFFERENTIATION
- Volume
- 13
- Number
- 10
- Start Page
- 1641
- End Page
- 1650
- URI
- http://scholarworks.bwise.kr/ssu/handle/2018.sw.ssu/6140
- DOI
- 10.1038/sj.cdd.4401855
- ISSN
- 1350-9047
- Abstract
- Death receptors in the TNF receptor superfamily signal for apoptosis via the ordered recruitment of FADD and caspase-8 to a death-inducing signaling complex ( DISC). However, the nature of the protein-protein interactions in the signaling complex is not well defined. Here we show that FADD self-associates through a conserved RXDLL motif in the death effector domain (DED). Despite exhibiting similar binding to both Fas and caspase-8 and preserved overall secondary structure, FADD RDXLL motif mutants cannot reconstitute FasL- or TRAIL-induced apoptosis and fail to recruit caspase-8 into the DISC of reconstituted FADD-deficient cells. Abolishing self-association can transform FADD into a dominant-negative mutant that interferes with Fas-induced apoptosis and formation of microscopically visible receptor oligomers. These findings suggest that lateral interactions among adapter molecules are required for death receptor apoptosis signaling and implicate self-association into oligomeric assemblies as a key function of death receptor adapter proteins in initiating apoptosis.
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Collections - College of Natural Sciences > Department of Chemistry > 1. Journal Articles
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