A novel protein domain required for apoptosis. Mutational analysis of human Fas antigen

J Biol Chem. 1993 May 25;268(15):10932-7.


The Fas antigen is a cell surface protein that can mediate apoptosis and that belongs to the tumor necrosis factor receptor family. Murine fibroblast L929 cells or T-cell lymphoma WR19L cells expressing the human Fas antigen were killed within 4-6 h by anti-human Fas antibody in a concentration-dependent manner. Human Fas antigen cDNAs with various mutations in the cytoplasmic region were constructed and expressed in L929 cells. A deletion of 15 amino acids from the C terminus of the Fas antigen enhanced the Fas antibody-induced killing activity, whereas a further deletion abolished its activity. This suggests the presence of an inhibitory as well as a signal-transducing domain in the cytoplasmic region of the Fas antigen. A 68-amino acid portion of the signal-transducing domain significantly conserved in the Fas antigen as well as in the type I tumor necrosis factor receptor was considered to be the novel protein domain required for apoptotic signal transduction.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal
  • Antigens, Surface / genetics*
  • Antigens, Surface / immunology
  • Antigens, Surface / metabolism*
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Base Sequence
  • Cell Death / drug effects
  • Humans
  • Kinetics
  • L Cells
  • Lymphoma, T-Cell
  • Mice
  • Molecular Sequence Data
  • Mutagenesis
  • Mutagenesis, Site-Directed
  • Oligodeoxyribonucleotides
  • Polymerase Chain Reaction
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Restriction Mapping
  • Sequence Deletion
  • Sequence Homology, Amino Acid
  • Transfection
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / pharmacology
  • fas Receptor


  • Antibodies, Monoclonal
  • Antigens, Surface
  • Oligodeoxyribonucleotides
  • Receptors, Cell Surface
  • Tumor Necrosis Factor-alpha
  • fas Receptor