Source:http://linkedlifedata.com/resource/pubmed/id/12690108
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
26
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pubmed:dateCreated |
2003-6-23
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pubmed:abstractText |
CD47 is a surface receptor that induces either coactivation or apoptosis in lymphocytes, depending on the ligand(s) bound. Interestingly, the apoptotic pathway is independent of caspase activation and cytochrome c release and is accompanied by early mitochondrial dysfunction with suppression of mitochondrial membrane potential (Deltapsim). Using CD47 as bait in a yeast two-hybrid system, we identified the Bcl-2 homology 3 (BH3)-only protein 19 kDa interacting protein-3 (BNIP3), a pro-apoptotic member of the Bcl-2 family, as a novel partner. Interaction between CD47 and the BH3-only protein was confirmed by immunoprecipitation analysis, and CD47-induced apoptosis was inhibited by attenuating BNIP3 expression with antisense oligonucleotides. Finally, we showed that the C-terminal domain of thrombospondin-1 (TSP-1), but not signal-regulatory protein (SIRPalpha1), is the ligand for CD47 involved in inducing cell death. Immunofluorescence analysis of CD47 and BNIP3 revealed a partial colocalization of both molecules under basal conditions. After T cell stimulation via CD47, BNIP3 translocates to the mitochondria to induce apoptosis. These results show that the BH3-dependent apoptotic pathways, previously shown to be activated by intracellular pro-apoptotic events, can also be turned on by surface receptors. This new pathway results in a fast induction of cell death resembling necrosis, which is likely to play an important role in lymphocyte regulation at inflammatory sites and/or in the vicinity of thrombosis.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD47,
http://linkedlifedata.com/resource/pubmed/chemical/BNIP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/BNIP3L protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CD47 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Thrombospondin 1,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
27
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
23915-21
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:12690108-Antigens, CD,
pubmed-meshheading:12690108-Antigens, CD47,
pubmed-meshheading:12690108-Apoptosis,
pubmed-meshheading:12690108-Carrier Proteins,
pubmed-meshheading:12690108-Humans,
pubmed-meshheading:12690108-Jurkat Cells,
pubmed-meshheading:12690108-Membrane Proteins,
pubmed-meshheading:12690108-Mitochondria,
pubmed-meshheading:12690108-Protein Transport,
pubmed-meshheading:12690108-Proto-Oncogene Proteins,
pubmed-meshheading:12690108-Signal Transduction,
pubmed-meshheading:12690108-Solubility,
pubmed-meshheading:12690108-T-Lymphocytes,
pubmed-meshheading:12690108-Thrombospondin 1,
pubmed-meshheading:12690108-Tumor Suppressor Proteins,
pubmed-meshheading:12690108-Two-Hybrid System Techniques
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pubmed:year |
2003
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pubmed:articleTitle |
CD47 and the 19 kDa interacting protein-3 (BNIP3) in T cell apoptosis.
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pubmed:affiliation |
Unité INSERM 576 et Laboratoire d'Immunologie, 06202 Nice cedex 3, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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