Figure 3

TNFR-mediated apoptosis. TNFR-I upon interaction with TNF-α undergo trimerization and recruitment of TNFR-associated death domain (TRADD), TNFR-associated factor 2 (TRAF-2) and receptor-interacting protein (RIP) to form complex I. This complex activates NF-κB via phosphorylation of IKK and IκB. NF-κB inhibits apoptosis by inducing a number of ant-apoptotic molecules (Bcl-xL, cIAPs, FLIP, Gadd45β, A20). After internalization of TNFR-I, TRADD, TRAF 2, and RIP are dissociated from the complex and FADD and caspase-8 are recruited (Complex II) to induce apoptosis. TRAF2 also activate JNK and sustanin activation of JNK induces apoptosis via selective release of Smac from the mitochondria.