Abstract
We report here the identification and functional characterization of two new human caspase recruitment domain (CARD) molecules, termed Pseudo-interleukin-1beta converting enzyme (ICE) and ICEBERG. Both proteins share a high degree of homology, reaching 92% and 53% identity, respectively, to the prodomain of caspase-1/ICE. Interestingly, both Pseudo-ICE and ICEBERG are mapped to chromosome 11q22 that bears caspases-1, -4- and -5 genes, all involved in cytokine production rather than in apoptosis. We demonstrate that Pseudo-ICE and ICEBERG interact physically with caspase-1 and block, in a monocytic cell line, the interferon-gamma and lipopolysaccharide-induced secretion of interleukin-1beta which is a well-known consequence of caspase-1 activation. Moreover, Pseudo-ICE, but not ICEBERG, interacts with the CARD-containing kinase RICK/RIP2/CARDIAK and activates NF-kappaB. Our data suggest that Pseudo-ICE and ICEBERG are intracellular regulators of caspase-1 activation and could play a role in the regulation of IL-1beta secretion and NF-kappaB activation during the pro-inflammatory cytokine response.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Apoptosis / drug effects
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Base Sequence
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Carrier Proteins / chemistry*
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Caspase 1 / chemistry
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Caspase 1 / metabolism
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Caspase Inhibitors
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Caspases / chemistry*
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Caspases / genetics
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Caspases / metabolism*
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Cell Line
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Cloning, Molecular
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Enzyme Activation
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Humans
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Interferon-gamma / antagonists & inhibitors
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Interferon-gamma / pharmacology
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Interleukin-1 / biosynthesis*
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Interleukin-1 / metabolism
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Intracellular Signaling Peptides and Proteins*
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Lipopolysaccharides / antagonists & inhibitors
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Lipopolysaccharides / pharmacology
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Molecular Sequence Data
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NF-kappa B / metabolism
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Protein Binding
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Protein Kinases / metabolism
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Receptor-Interacting Protein Serine-Threonine Kinase 2
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Receptors, Interleukin-1 / antagonists & inhibitors
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Sequence Alignment
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Tumor Necrosis Factor-alpha / pharmacology
Substances
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CARD18 protein, human
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Carrier Proteins
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Caspase Inhibitors
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Interleukin-1
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Intracellular Signaling Peptides and Proteins
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LLID-114769 protein, human
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Lipopolysaccharides
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NF-kappa B
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Receptors, Interleukin-1
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Tumor Necrosis Factor-alpha
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Interferon-gamma
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Protein Kinases
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RIPK2 protein, human
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Receptor-Interacting Protein Serine-Threonine Kinase 2
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Caspases
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Caspase 1