THE cell-killing effects of the cytokines TNF-alpha and Fast are media
ted 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(1-4). The cytoplasmic r
egions 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-kappa B (refs 5, 6). Here w
e report the isolation of a 54K receptor that is a new member of the T
NFR superfamily, using the death domain of TNFR1 in a yeast two-hybrid
system(7,8). This protein, WSL-1, is most similar to TNFR1 itself, pa
rticularly in the death-domain region, The gene wsl-1 is capable of in
ducing apoptosis when transfected into 3T3 and 293 cells, and can also
activate NF-kappa B in 293 cells, Like TNFR1, WSL-1 will homodimerize
in yeast. WSL-1 also interacts specifically with the TNFR1-associated
molecule TRADD(9). The tissue distribution is very restricted and sig
nificantly different from that of Fas and TNFR1.