Identification of CARDIAK, a RIP-like kinase that associates with caspase-1

Members of the tumor necrosis factor receptor (TNFR) superfamily have an important role in the induction of cellular signals resulting in cell growth, differentiation and death [1], TNFR-1 recruits and assembles a signaling complex containing a number of death domain (DD)-containing proteins, including the adaptor protein TRADD and the serine/threonine kinase RIP [2], which mediates TNF-induced NF-kappa B activation [3]. RIP also recruits caspase-2 to the TNFR-1 signaling complex via the adaptor protein RAIDD, which contains a DD and a caspase-recruiting domain (CARD) [4], Here, we have identified a RIP-like kinase, termed CARDIAK (for CARD-containing interleukin(IL)-1 beta converting enzyme (ICE) associated kinase), which contains a serine/threonine kinase domain and a carboxy-terminal CARD [5], Overexpression of CARDIAK induced the activation of both NF-kappa B and Jun N-terminal kinase (JNK), CARDIAK interacted with the TNFR-associated factors TRAP-1 and TRAF-5, and a dominant-negative form of TRAF-2 inhibited CARDIAK induced NF-kappa B activation, Interestingly, CARDIAK specifically interacted with the CARD of caspase-1 (previously known as ICE), and this interaction correlated with the processing of pro-caspase-1 and the formation of the active p20 subunit of caspase-1, Together, these data suggest that CARDIAK may be involved in NF-kappa B/JNK signaling and in the generation of the proinflammatory cytokine IL-1 beta through activation of caspase-1.