Caspase recruitment domains for protein interactions in cellular signaling (Review)

The caspase recruitment domain (CARD), a well-known protein interaction module, belongs to the death domain (DD) superfamily, which includes DDs, death effector domains, and pyrin domains. The DD superfamily mediates the protein interactions necessary for apoptosis and immune cell signaling pathways. Among these domains, the CARD has been studied extensively as it mediates important cellular signaling events that are associated with various human diseases including cancer, neuro-degenerative diseases and immune disorders. Homo-type and hetero-type CARD-CARD interactions mediate the formation of large signaling complexes, including caspase-activating complexes and downstream signaling complexes. The present review summarizes and discusses the results of structural studies of various CARDs and their complexes. These studies shed light on the mechanisms that control the assembly and disassembly of signaling complexes and provide an improved understanding of cellular signaling processes.