title: FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis.
abstract: 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.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor 48109, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Chinnaiyan
authors.forename: K
authors.initials: K
authors.lastname: O'Rourke
authors.forename: M
authors.initials: M
authors.lastname: Tewari
authors.forename: V M
authors.initials: VM
authors.lastname: Dixit
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D053200:Fas-Associated Death Domain Protein; D006801:Humans; D008969:Molecular Sequence Data; D017354:Point Mutation; D012441:Saccharomyces cerevisiae; D015843:Serpins / Q000494:pharmacology; D015398:Signal Transduction; D014764:Viral Proteins; D019014:fas Receptor
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000954:Antigens, Surface; D002352:Carrier Proteins; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D015843:Serpins; D014764:Viral Proteins; D019014:fas Receptor; C074641:interleukin-1beta-converting enzyme inhibitor