Caspase activating and recruitment domain 8 protein (CARD8, also known as TUCAN, CARDINAL) has been implicated as a regulator of several pro-inflammatory and apoptotic signaling pathways. The C-terminal CARD domain of CARD8 (TUCAN) binds procaspase-9 (CASP9(1-416)) and interferes with binding of APAF1 to procaspase-9 thus suppressing caspase activation induced by the APAF1:cytochrome c (CYCS) axis (Pathan N et al. 2001). The structural studies of CARD8 suggest that in addition to intermolecular CARD-CARD interactions, CARD domain may intramolecularly associate with the N-terminal function to find domain (FIIND) to regulate apoptotic and inflammatory signaling pathways (Jin T et al. 2013).

Several binding partners of CARD8 have been reported. CARD8 can interact physically via CARD domain with caspase-1 and negatively regulates caspase-1-dependent IL-1beta generation in the THP-1 monocytic cell line (Razmara M et al. 2002). The FIIND domain of CARD8 may inhibit NFkappaB activation, possibly through interaction with IKKgamma (Bouchier-Hayes L et al. 2001). FIIND may also bind the nucleotide-binding domain (NBD) domain of NOD2 and NLRP3 to regulate the immune response to bacterial infections (Kampen O et al. 2010).

High levels of CARD8 expression have been observed in several tumor cell lines and malignant specimens from human patients underlying its importance in regulating inflammatory and apoptotic pathways (Bouchier-Hayes L et al. 2001; Pathan N et al. 2001; Razmara M et al. 2002; Zhang H & Fu W 2002; Yamamoto M et al. 2005).