Regulation of IL-1 beta generation by Pseudo-ICE and ICEBERG, two dominantnegative caspase recruitment domain proteins

We report here the identification and functional characterization of two ne w human caspase recruitment domain (CARD) molecules, termed Pseudo-interleu kin-1 beta converting enzyme (ICE) and ICEBERG. Both proteins share a high degree of homology, reaching 92% and 53% identity, respectively, to the pro domain of caspase-1/ICE. Interestingly, both Pseudo-ICE and ICEBERG are map ped to chromosome 11q22 that bears caspases-1, -4- and -5 genes, all involv ed in cytokine production rather than in apoptosis, We demonstrate that Pse udo-ICE and ICEBERG interact physically with caspase-1 and block, in a mono cytic cell line, the interferon-ii and lipopolysaccharide induced secretion of interleukin-1 beta which is a well-known consequence of caspase-1 activ ation. Moreover, Pseudo-ICE, but not ICEBERG, interacts with the CARD-conta ining kinase RICK/RIP2/CARDIAK and activates NF-kappaB. Our data suggest th at Pseudo-ICE and ICEBERG are intracellular regulators of caspase-1 activat ion and could play a role in the regulation of IL-1 beta secretion and NF-k appaB activation du ring the pro-inflammatory cytokine response.