Caspase Recruitment Domain (CARD) as a Bi-functional Switch of Caspase Regulation and NF-κB Signals

Over the last three years, increasing numbers of adaptor molecules that contain the caspase recruitment domain (CARD) have been identified.CARD was originally described as a protein-binding motif that interacts with caspase through a CARD-CARD interaction.However, CARD has now also been found in many adaptor proteins that do not interact with caspase, but mediate the assembly of CARD-containing proteins in apoptosis and NF-κB signaling.Apoptotic signaling is controlled by homo-and heterophilic interactions between CARD-containing molecules: Caspases exist as inactive zymogens, and are activated through interactions with adaptor molecules that contain CARD.CARD-containing molecules are also involved in the regulation of gene expression that is involved in cell survival and immune responses through NF-κB activation.Therefore, this report will describe the function and signaling cascade of recently identified CARD-containing proteins in apoptosis and NF-κB activation.CARD-containing molecules were divided into two major groups, based on their functional interactions with caspase and NF-κB signals (Fig. 1 and Table 1). CARD-adaptor in NF-κB activation Frequent mutation in tumors affecting NF-κB activation and apoptosisBcl10/CLAP/CIPER/mE10/CARMEN Bcl10 was recently cloned from the chromosome translocation t (1; 14) (p22; q32) in MALT B cell lymphoma.Inactivating mutations and the over-expression of Bcl10 were also frequently found in the lymphoid tumor of the B or T cell lineage, as well as cell lines that are derived from solid tumor types (Fakruddin et al.,