A death-domain-containing receptor that mediates apoptosis

Nature. 1996 Nov 28;384(6607):372-5. doi: 10.1038/384372a0.


The cell-killing effects of the cytokines TNF-alpha and FasL are mediated by the distinct cell-surface receptors TNFR1, TNFR2 and Fas (also known as CD95/APO-1), which are all members of a receptor superfamily that is important for regulating cell survival. The cytoplasmic regions of TNFR1 and Fas contain a conserved 'death' domain which is an essential component of the signal pathway that triggers apoptosis and activation of the transcription factor NF-kappaB (refs 5,6). Here we report the isolation of a 54K receptor that is a new member of the TNFR superfamily, using the death domain of TNFR1 in a yeast two-hybrid system. This protein, WSL-1, is most similar to TNFR1 itself, particularly in the death-domain region. The gene wsl-1 is capable of inducing apoptosis when transfected into 3T3 and 293 cells, and can also activate NF-kappaB in 293 cells. Like TNFR1, WSL-1 will homodimerize in yeast. WSL-1 also interacts specifically with the TNFR1-associated molecule TRADD. The tissue distribution is very restricted and significantly different from that of Fas and TNFR1.

MeSH terms

  • Amino Acid Sequence
  • Antigens, CD / chemistry
  • Apoptosis*
  • Cell Line
  • Cloning, Molecular
  • Conserved Sequence*
  • Humans
  • Molecular Sequence Data
  • Mutagenesis
  • Protein Binding
  • Receptors, Tumor Necrosis Factor / chemistry
  • Receptors, Tumor Necrosis Factor, Member 25
  • Receptors, Tumor Necrosis Factor, Type I
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Transfection


  • Antigens, CD
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Member 25
  • Receptors, Tumor Necrosis Factor, Type I
  • TNFRSF25 protein, human

Associated data

  • GENBANK/Y09392