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

Mohamed Lamkanfi; Geertrui Denecker; Michael Kalai; Kathleen D'hondt; Ann Meeus; Wim Declercq; Xavier Saelens; Peter Vandenabeele

doi:10.1074/jbc.M407891200

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

J Biol Chem. 2004 Dec 10;279(50):51729-38. doi: 10.1074/jbc.M407891200. Epub 2004 Sep 21.

Authors

Mohamed Lamkanfi¹, Geertrui Denecker, Michael Kalai, Kathleen D'hondt, Ann Meeus, Wim Declercq, Xavier Saelens, Peter Vandenabeele

Affiliation

¹ Unit of Molecular Signalling and Cell Death, Department for Molecular Biomedical Research, VIB-Ghent University, Technologiepark 927, Zwijnaarde B-9052, Belgium.

PMID: 15383541
DOI: 10.1074/jbc.M407891200

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing
Amino Acid Sequence
Base Sequence
Carrier Proteins / genetics
Carrier Proteins / physiology*
Caspase 1
Caspases / chemistry
Caspases / genetics
Caspases / metabolism
Cell Line
Chromosome Mapping
Chromosomes, Human, Pair 11 / genetics
DNA, Complementary / genetics
Enzyme Precursors / chemistry
Enzyme Precursors / genetics
Enzyme Precursors / metabolism
Gene Expression
Humans
In Vitro Techniques
Interferon-gamma / pharmacology
Interleukin-1 / biosynthesis*
Molecular Sequence Data
NF-kappa B / metabolism
Protein Structure, Tertiary
RNA, Messenger / genetics
RNA, Messenger / metabolism
Recombinant Proteins
Sequence Homology, Amino Acid
Signal Transduction
Tissue Distribution
U937 Cells
Up-Regulation / drug effects

Substances

Adaptor Proteins, Signal Transducing
CARD17 protein, human
Carrier Proteins
DNA, Complementary
Enzyme Precursors
Interleukin-1
NF-kappa B
RNA, Messenger
Recombinant Proteins
Interferon-gamma
Caspases
Caspase 1

Associated data

GENBANK/AY761064