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. 2013 Spring;13(1):119–130.

Figure 2.

Figure 2.

Signal transduction by TNF-α leads to apoptosis or necroptosis. Invagination of Complex 1 results in the formation of Complex 2a (apoptosome) or 2b (necroptosome). Soluble TNF-α binds to its cognate receptor, TNFR1, which is bound to SODD via the TNFR1 DD. Binding of TNF-α to TNFR1 releases SODD, enabling the binding of TRADD, followed by the assembly of RIP1, TRAF2/5, and cIAP1/2. Endocytosis of Complex 1 leads to the degradation of cIAP1/2 and the formation of Complex 2a, which consists of TRADD, TRAF2/5, RIP1, FADD, and the zymogens procaspase-8 and -10. Procaspase-8 and -10 are cleaved, and caspase-8 and -10 cleave BID into tBID, activating the mitochondrial death pathway. Caspase-8 and -10 also activate caspase-3, -6, and -7, leading to apoptosis.