THE TNF RECEPTOR 1-ASSOCIATED PROTEIN TRADD SIGNALS CELL-DEATH AND NF-KAPPA-B ACTIVATION

Many diverse activities of tumor necrosis factor (TNF) are signaled through TNF receptor 1 (TNFR1). We have identified a novel 34 kDa protein, designated TRADD, that specifically interacts with an intracellular domain of TNFR1 known to be essential for mediating programmed cell death. Overexpression of TRADD leads to two major TNF-induced responses, apoptosis and activation of NF-kappa B. The C-terminal 118 amino acids of TRADD are sufficient to trigger both of these activities and likewise sufficient for interaction with the death domain of TNFR1. TRADD-mediated cell death can be suppressed by the crmA gene, which encodes a specific inhibitor of the interleukin-1 beta-converting enzyme. However, NF-kappa B activation by TRADD is not inhibited by crmA expression, demonstrating that the signaling pathways for TNF-induced cell death and NF-kappa B activation are distinct.