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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
16
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pubmed:dateCreated |
2002-4-15
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pubmed:databankReference |
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pubmed:abstractText |
Caspase-associated recruitment domains (CARD) are protein-protein interaction modules found extensively in proteins that play important roles in apoptosis, NFkappaB activation, and cytokine regulation. In this study we identified a novel human protein, CARD-8, which contains a C-terminal CARD domain with high similarity to the CARD domain of caspase-1/ICE. We demonstrate that CARD-8 interacts physically with caspase-1 and negatively regulates caspase-1-dependent IL-1beta generation in the THP-1 monocytic cell line. CARD-8 binds also to ICEBERG and pseudo-ICE, two other recently identified proteins, which bind to the CARD domain of caspase-1 and negatively regulate its activity. Reverse transcriptase-PCR analysis revealed that CARD-8 is expressed mainly in monocytes, placenta, lymph nodes, and spleen. This pattern of expression is consistent with caspase-1 expression in the same cells and tissues. CARD-8 was also found to negatively regulate NF-kappaB activation by TNF-alpha stimulation and by ectopically expressed RICK, suggesting that this protein may control cell survival. Consistent with these results, stable expression of CARD-8 in U937 or THP-1 cells sensitizes the cells to differentiation-induced apoptosis. Overexpression of CARD-8 can also induce apoptosis in transfected cells. The results suggest that CARD-8 represents a new signaling molecule involved in the regulation of caspase-1 and NF-kappaB activation.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/CARD Signaling Adaptor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/CARD8 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 1,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nucleoside-Phosphate Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
19
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pubmed:volume |
277
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
13952-8
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:11821383-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:11821383-Amino Acid Sequence,
pubmed-meshheading:11821383-Apoptosis,
pubmed-meshheading:11821383-CARD Signaling Adaptor Proteins,
pubmed-meshheading:11821383-Carrier Proteins,
pubmed-meshheading:11821383-Caspase 1,
pubmed-meshheading:11821383-Cell Line,
pubmed-meshheading:11821383-DNA, Complementary,
pubmed-meshheading:11821383-Enzyme Activation,
pubmed-meshheading:11821383-Humans,
pubmed-meshheading:11821383-Interleukin-1,
pubmed-meshheading:11821383-Luciferases,
pubmed-meshheading:11821383-Molecular Sequence Data,
pubmed-meshheading:11821383-NF-kappa B,
pubmed-meshheading:11821383-Neoplasm Proteins,
pubmed-meshheading:11821383-Nucleoside-Phosphate Kinase,
pubmed-meshheading:11821383-Precipitin Tests,
pubmed-meshheading:11821383-Protein Structure, Tertiary,
pubmed-meshheading:11821383-RNA, Messenger,
pubmed-meshheading:11821383-Sequence Homology, Amino Acid,
pubmed-meshheading:11821383-Time Factors,
pubmed-meshheading:11821383-Tissue Distribution,
pubmed-meshheading:11821383-Transfection,
pubmed-meshheading:11821383-Tumor Cells, Cultured,
pubmed-meshheading:11821383-Tumor Necrosis Factor-alpha
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pubmed:year |
2002
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pubmed:articleTitle |
CARD-8 protein, a new CARD family member that regulates caspase-1 activation and apoptosis.
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pubmed:affiliation |
Center for Apoptosis Research and the Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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