FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis

Cell. 1995 May 19;81(4):505-12. doi: 10.1016/0092-8674(95)90071-3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Sequence
  • Antigens, Surface / genetics
  • Antigens, Surface / metabolism*
  • Apoptosis*
  • Base Sequence
  • Binding Sites / genetics
  • Carrier Proteins / genetics
  • Carrier Proteins / isolation & purification*
  • Carrier Proteins / metabolism
  • Cell Line
  • Cloning, Molecular
  • Fas-Associated Death Domain Protein
  • Humans
  • Molecular Sequence Data
  • Point Mutation
  • Saccharomyces cerevisiae
  • Serpins / pharmacology
  • Signal Transduction
  • Viral Proteins*
  • fas Receptor


  • Adaptor Proteins, Signal Transducing
  • Antigens, Surface
  • Carrier Proteins
  • FADD protein, human
  • Fas-Associated Death Domain Protein
  • Serpins
  • Viral Proteins
  • fas Receptor
  • interleukin-1beta-converting enzyme inhibitor

Associated data

  • GENBANK/U24231