Caspase-8 and -10 mediated induction of NF-kB

Stable Identifier
R-GGA-1227739
Type
Pathway
Species
Gallus gallus
Related Species
Infectious bronchitis virus
ReviewStatus
5/5
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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].

Literature References
PubMed ID Title Journal Year
16585540 Roles of caspase-8 and caspase-10 in innate immune responses to double-stranded RNA

Kawai, T, Sato, S, Kumar, H, Akira, S, Yonehara, S, Takahashi, K

J Immunol 2006
16618810 Caspases leave the beaten track: caspase-mediated activation of NF-kappaB

Vandenabeele, P, Vanden Berghe, T, Lamkanfi, M, Declercq, W

J Cell Biol 2006
12884866 Caspase-8 and caspase-10 activate NF-kappaB through RIP, NIK and IKKalpha kinases

Miyashita, T, Shikama, Y, Yamada, M

Eur J Immunol 2003
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