A death-domain-containing receptor that mediates apoptosis

• Published in: Nature (London) Vol. 384; no. 6607; pp. 372 - 375
• Main Authors: Kitson, Jeremy, Raven, Thomas, Jiang, Ying-Ping, Goeddel, David V, Giles, Katharine M, Pun, Kwok-Tao, Grinham, Christine J, Brown, Robin, Farrow, Stuart N
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 28-11-1996; Nature Publishing Group
• Subjects: Ageing, cell death; Amino Acid Sequence; Antigens, CD - chemistry; Apoptosis; Biological and medical sciences; Cell Line; Cell physiology; Cloning, Molecular; Conserved Sequence; Fundamental and applied biological sciences. Psychology; Humans; Molecular and cellular biology; Molecular Sequence Data; Mortality; 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; Yeasts; Human; Nucleotide sequence; Tissue specificity; Homology; Gene expression; Binding protein; Signal transduction; Cell line; Complementary DNA; Gene; Domain structure; Tumor necrosis factor; Multigene family; Apoptosis; Biological receptor
• ISSN: 0028-0836; 1476-4687
• 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.