In mammals, virus-triggered RIG-1 or MDA5 receptor complex has been shown to recruit initiator caspases-8 and -10 via adapter FADD (Fas-associated death domain-containing protein) leading to NF-kB activation [Takahashi K et al 2006]. Other FADD and caspase-interacting adaptors - RIP-1(receptor interacting protein-1) and TRADD (TNFR-associated death domain) - have been also implicated in RLR-dependent antiviral responses [Kawai T et al 2005, Balachandran M et al 2004, Michallet MC et al 2008]. FADD, TRADD and RIP-1 form signaling complexes that coordinate both apoptotic and non-apoptotic functions of caspases.
It has been suggested that large prodomains with DED (death effector domains) of caspases-8/10 can function as a bridge to link downstream mediators like IKK complex to the adaptor proteins [Chaudhary PM et al 2000, Lamkanfi M et al 2006]. Recruitment of caspases-8/10 to activated receptor complex is also believed to result in conformational changes leading to caspase auto-proteolysis. Processed caspases were shown to activate NF-kB signaling. However, the detailed mechanism of caspase-mediated NF-kB induction remains unclear [Takahashi K et al 2006, Lamkanfi M et al 2006].