J Biol Chem. 2004 Dec 10;279(50):51729-38. Epub 2004 Sep 21.
INCA, a novel human caspase recruitment domain protein that inhibits interleukin-1beta generation.
Lamkanfi, M., Denecker, G., Kalai, M., D'hondt, K., Meeus, A., Declercq, W., Saelens, X., Vandenabeele, P.,
--- - Unit of Molecular Signalling and Cell Death, Department for Molecular Biomedical Research, VIB-Ghent University, Technologiepark 927, Zwijnaarde B-9052, Belgium.
--- - Unit of Molecular Signalling and Cell Death, Department for Molecular Biomedical Research, VIB-Ghent University, Technologiepark 927, Zwijnaarde B-9052, Belgium.
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 ICEBERG, 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-gamma in the monocytic cell lines THP-1 and U937. INCA physically interacts with procaspase-1 and blocks the release of mature IL-1beta from LPS-stimulated macrophages. Unlike COP/Pseudo-ICE and procaspase-1, INCA does not interact with RIP2 and does not induce NF-kappaB activation. Our data show that INCA is a novel intracellular regulator of procaspase-1 activation, involved in the regulation of pro-IL-1beta processing and its release during inflammation.
PMID: 15383541

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In vivo interaction | |||||||||||||
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Endogenous expression |
Overexpression | DD1 | DD2 | Reference | |||||||||
Family | DD1 | DD2 | Method | Species | Region | Species | Region | ||||||
CARD | CARD16 |
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CARD17 | Co-immunoprecipitation | HEK293 | Human | 1-106 | Human | Not specified | 15383541 | |||
CARD | CARD17 |
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CARD17 | Co-immunoprecipitation | HEK293 | Human | Not specified | Human | Not specified | 15383541 | |||
CARD | CARD17 |
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CARD18 | Co-immunoprecipitation | HEK293 | Human | Not specified | Human | Full length | 15383541 | |||
CARD | CARD17 |
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Caspase1 | Co-immunoprecipitation | HEK293 | Human | Not specified | Not specified | Not specified | 15383541 |
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