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Abstract
Tumor necrosis factor (TNF) can induce apoptosis and activate NF-kappa B through signaling
cascades emanating from TNF receptor 1 (TNFR1). TRADD is a TNFR1-associated signal
transducer that is involved in activating both pathways. Here we show that TRADD directly
interacts with TRAF2 and FADD, signal transducers that activate NF-kappa B and induce
apoptosis, respectively. A TRAF2 mutant lacking its N-terminal RING finger domain
is a dominant-negative inhibitor of TNF-mediated NF-kappa B activation, but does not
affect TNF-induced apoptosis. Conversely, a FADD mutant lacking its N-terminal 79
amino acids is a dominant-negative inhibitor of TNF-induced apoptosis, but does not
inhibit NF-kappa B activation. Thus, these two TNFR1-TRADD signaling cascades appear
to bifurcate at TRADD.