Curr Biol. 1998 Jul 16;8(15):885-8.

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

Thome, M., Hofmann, K., Burns, K., Martinon, F., Bodmer, J. L., Mattmann, C., Tschopp, J.,
--- - Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.
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. 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, which mediates TNF-induced NF-kappa B activation. 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). 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. Overexpression of CARDIAK induced the activation of both NF-kappa B 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-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.
PMID: 9705938External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
CARD Caspase1 Link RIPK2 Co-immunoprecipitation HEK293 Human 2-540 Human 2-92 9705938
CARD CIAP1 Link RIPK2 Co-immunoprecipitation HEK293 Not specified Not specified Human 2-540 9705938
CARD CIAP2 Link RIPK2 Co-immunoprecipitation HEK293 Not specified Not specified Human 2-540 9705938
(Link: click this icon to show interactions only between the two corresponding DDs)
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
Functional Role
Family DD1 DD2 Method Death-related Death-unrelated Reference
CARD Caspase1 Link RIPK2 Caspase cleaved assay Pro-caspase1 activation 9705938
(Link: click this icon to show interactions only between the two corresponding DDs)