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INCA, a novel human caspase recruitment domain protein that inhibits interleukin-1β generation

par Lamkanfi, Mohamed;Denecker, Geertrui;Kalai, Michaël ;D'Hondt, Kathleen;Meeus, Ann;Declercq, Wim;Saelens, Xavier;Vandenabeele, Peter
Référence The Journal of biological chemistry, 279, 50, page (51729-51738)
Publication Publié, 2004-12

Article révisé par les pairs

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Résumé :

Using in silico methods for screening the human genome for new caspase recruitment domain (CARD) proteins, we have identified INCA (Inhibitory CARD) as a protein that shares 81% identity with the prodomain of caspase-1. The INCA gene is located on chromosome 11q22 between the genes of COP/Pseudo-ICE and ICE-BERG, two other CARD proteins that arose from caspase-1 gene duplications. We show that INCA mRNA is expressed in many tissues. INCA is specifically upregulated by interferon-γ in the monocytic cell lines THP-1 and U937. INCA physically interacts with procaspase-1 and blocks the release of mature IL-1β from LPS-stimulated macrophages. Unlike COP/Pseudo-ICE and procaspase-1, INCA does not interact with RIP2 and does not induce NF-κB activation. Our data show that INCA is a novel intracellular regulator of procaspase-1 activation, involved in the regulation of pro-IL-1β processing and its release during inflammation.