AI Article Synopsis
- Researchers used computer-based methods to search the human genome for new proteins and discovered a protein called INCA (Inhibitory CARD) that is closely related to the prodomain of caspase-1.
- The INCA gene is on chromosome 11q22 and is expressed in various tissues; it increases in response to interferon-gamma in certain immune cell lines.
- INCA interacts with procaspase-1 to prevent the release of the inflammatory molecule IL-1beta from macrophages and serves as a unique regulator of caspase-1 activation without affecting other related proteins.
Article Abstract
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.
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| http://dx.doi.org/10.1074/jbc.M407891200 | DOI Listing |
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