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

By Margot Thome, Kay Hofmann, Kim Burns, Fabio Martinon, Jean-Luc Bodmer, Chantal Mattmann and Jürg Tschopp


AbstractMembers 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-κB 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)-1β 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-κB and Jun N-terminal kinase (JNK). CARDIAK interacted with the TNFR-associated factors TRAF-1 and TRAF-2 and a dominant-negative form of TRAF-2 inhibited CARDIAK-induced NF-κB 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-κwB/JNK signaling and in the generation of the proinflammatory cytokine IL-1β through activation of caspase-1

Publisher: Elsevier Science Ltd.
Year: 1998
DOI identifier: 10.1016/S0960-9822(07)00352-1
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