TNF-induced signaling in apoptosis

Out of the almost 17 members of the TNF superfamily, TNF is probably the mo st potent inducer of apoptosis. TNF activates both cell-survival and cell-d eath mechanisms simultaneously. Activation of NF-kB-dependent genes regulat es the survival and proliferative effects pf TNF, whereas activation of cas pases regulates the apoptotic effects. TNF-induced apoptosis is mediated pr imarily through the activation of type I receptors, the death domain of whi ch recruits more than a dozen different signaling proteins, which together are considered part of an apoptotic cascade. This cascade does not, however , account for the role of reactive oxygen intermediates, ceramide, phosphol ipases, and serine proteases which are also implicated in TNF-induced apopt osis. This cascade also does not explain how type II TNF receptors which la ck the death domain, induce apoptosis. Nevertheless, this review of apoptos is signaling will be limited to those proteins that makeup the cascade.