Modulation of life and death by the TNF receptor superfamily

The tumor necrosis factor receptor (TNFR) superfamily represents a growing family, with over 20 members having been identified thus far in mammalian c ells. These proteins share significant homologies in their extracellular li gand binding domains and intracellular effector (death) domains. These rece ptors appear to transmit their signals via protein-protein interactions, wh ich convey either a death or survival signal. Isolation and characterizatio n of death domain containing proteins (TRADD, FADD/MORT-1, RIP), TRAF domai n containing proteins (TRAF1-6) as well as new members and adaptor proteins such as DAXX have provided new insights to our understanding of signaling mechanisms associated with this family of receptors, While the death signal s seem to be associated,vith the activation of both the caspase and JUN kin ase pathways, the survival signals are mediated via the activation of the N F-kappa B pathway.