FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis.
Using the cytoplasmic domain of Fas in the yeast two-hybrid system, we have identified a novel interacting protein, FADD, which binds Fas and Fas-FD5, a mutant of Fas possessing enhanced killing activity, but not the functionally inactive mutants Fas-LPR and Fas-FD8. FADD contains a death domain homologous to the death domains of Fas and TNFR-1. A point mutation in FADD, analogous to the lpr mutation of Fas, abolishes its ability to bind Fas, suggesting a death domain to death domain interaction. Overexpression of FADD in MCF7 and BJAB cells induces apoptosis, which, like Fas-induced apoptosis, is blocked by CrmA, a specific inhibitor of the interleukin-1 beta-converting enzyme. These findings suggest that FADD may play an important role in the proximal signal transduction of Fas.
Pubmed ID: 7538907 RIS Download
Adaptor Proteins, Signal Transducing | Amino Acid Sequence | Antigens, CD95 | Antigens, Surface | Apoptosis | Base Sequence | Binding Sites | Carrier Proteins | Cell Line | Cloning, Molecular | Fas-Associated Death Domain Protein | Humans | Molecular Sequence Data | Point Mutation | Saccharomyces cerevisiae | Serpins | Signal Transduction | Viral Proteins