A novel domain within the 55 kd TNF receptor signals cell death

Cell. 1993 Sep 10;74(5):845-53. doi: 10.1016/0092-8674(93)90464-2.


Deletion mutagenesis of the intracellular region of the 55 kd TNF receptor (TNF-R1) identified an approximately 80 amino acid domain near the C-terminus responsible for signaling cytotoxicity. This domain shows weak homology with the intracellular domain of Fas antigen, a transmembrane polypeptide that can also initiate a signal for cytotoxicity. Alanine-scanning mutagenesis of TNF-R1 confirmed that many of the amino acids conserved with Fas antigen are critical for the cytotoxic signal. This region of TNF-R1-Fas homology is therefore likely to define a novel domain (death domain) that signals programmed cell death. Mutations within the death domain of TNF-R1 also disrupted its ability to signal anti-viral activity and nitric oxide (NO) synthase induction. In addition, large deletions in the membrane-proximal half of the intracellular domain did not block signaling of cytotoxicity or anti-viral activity but did block induction of NO synthase.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Avian Sarcoma Viruses / genetics
  • Cell Death / physiology*
  • Clone Cells
  • Humans
  • Interferon-gamma / pharmacology
  • L Cells
  • Mice
  • Molecular Sequence Data
  • Mutagenesis
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / physiology*
  • Receptors, Tumor Necrosis Factor
  • Recombinant Proteins / toxicity
  • Repetitive Sequences, Nucleic Acid
  • Sequence Deletion
  • Sequence Homology, Amino Acid
  • Signal Transduction*
  • Transfection
  • Tumor Necrosis Factor-alpha / toxicity*


  • Receptors, Cell Surface
  • Receptors, Tumor Necrosis Factor
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma