A death-domain-containing receptor that mediates apoptosis

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Abstract

THE cell-killing effects of the cytokines TNF-α 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 survival1–4. 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-KB (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 system7,8. 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-KB in 293 cells. Like TNFR1, WSL-1 will homodimerize in yeast. WSL-1 also interacts specifically with the TNFRl-associated molecule TRADD9. The tissue distribution is very restricted and significantly different from that of Fas and TNFR1.

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Kitson, J., Raven, T., Jiang, Y. et al. A death-domain-containing receptor that mediates apoptosis. Nature 384, 372–375 (1996) doi:10.1038/384372a0

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