Caspase 8 or 10 recruitment to IPS1 complex followed by their dimerization

Stable Identifier
Gallus gallus
Related Species
Infectious bronchitis virus
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Induction of inflammatory cytokines in response to poly(I:C) was reduced in caspase -8/10 deficient human embryonic kidney 293(HEK293) cells [Takahashi K et al 2006]. Mammalian caspase-8 and caspase 10 are two large prodomain initiator caspases consisting of two DEDs (death effector domain) through which they interact with the death domain containing adaptors. Caspases-8/10 also contain catalytic domain with highly conserved QACQG motif. Cys residue in the QACQG motif is involved in their catalytic activity.

Recruitment of caspases-8 and -10 to the activated receptor complexes is believed to result in procaspase homodimerization and conformational changes, that are followed by proteolytic cleavage [Chen M et al 2002, Boatright KM et al 2003, Keller N et al 2009]. Proteolytic processing of the caspases-8/10 is required to activate NFkB [Shikama Y et al 2003]. In addition, poly(I:C) stimulation induced the processing of caspase-8/10 in HEK293 cells [Takahashi K et al 2006]. The processing is thought to occur by the autocatalytic cross-cleavage [YangX et al 1998, Oberst A et al 2010, Chang DW et al 2003]. Further downstream signaling processes to NFkB activation are mediated by the DED-containing prodomains of caspases-8/10, but do not require their catalytic domain [Shikama Y et al 2003, Chaudhary PM et al 2000, Takahashi K et al 2006]. The detailed mechanism of caspase mediated NFkB activation remains unclear.

The formation of heterodimers with caspase's homologue FLIP has been reported to induce NFkB activation [Boatright KM et al 2004, Kataoka T et al 2005, Pop C et al 2011].

Predicted chicken caspase-8 and caspase-10 proteins show 51 and 44% overall amino acid sequence identity to their human orthologs respectively. Sequence alignment of chicken and human caspases-8 and -10 revealed that the catalytic QACQG motif is conserved in the chicken orthologs. Due to lack of structural data this project does not describe a processing of chicken caspases.

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