IAP antagonists bind to the cIAP1 BIR3 domain and induce a conformational rearrangement, which promotes rapid RING domain-mediated dimerization, auto-ubiquitylation and cIAP1 degradation via the ubiquitin–proteasome system.13,45 The IAPs function as molecular switches between pro-survival and pro-apoptotic pathways at the TNFR1 and the loss of cIAP1 by IAP antagonist treatment results in formation of a RIPK1:caspase-8 complex and activation of the extrinsic apoptotic pathway in a subset of cancer cell lines. This evidence concerns the gene CASP8 and cancer.