Recent advances in tumor necrosis factor and CD40 signaling

The past year has witnessed remarkable advances in the understanding of signaling by the two TNF (tumor necrosis factor) receptors, TNFR1 and TNFR2, and the related CD40 receptor. Adaptor molecules (termed TRAFs) have been identified that associate with TNFR2 and CD40 and function to modulate the signaling pathways. Significantly, TRAF2 mediates the activation of NF-kappa B by both receptors. Furthermore, a molecule called TRADD has been identified that associates with the cytoplasmic segment of TNFR1. TRADD, which contains a novel 'death domain' that binds to the corresponding death domain in the cytoplasmic segment of TNFR1, can mediate both activation of NF-kappa B and induction of apoptosis, the two major responses signaled by TNFR1.