rdf:type |
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lifeskim:mentions |
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pubmed:issue |
46
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pubmed:dateCreated |
2000-12-29
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pubmed:databankReference |
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pubmed:abstractText |
Smac/DIABLO is a mitochondrial protein that is released along with cytochrome c during apoptosis and promotes cytochrome c-dependent caspase activation by neutralizing inhibitor of apoptosis proteins (IAPs). We provide evidence that Smac/DIABLO functions at the levels of both the Apaf-1-caspase-9 apoptosome and effector caspases. The N terminus of Smac/DIABLO is absolutely required for its ability to interact with the baculovirus IAP repeat (BIR3) of XIAP and to promote cytochrome c-dependent caspase activation. However, it is less critical for its ability to interact with BIR1/BIR2 of XIAP and to promote the activity of the effector caspases. Consistent with the ability of Smac/DIABLO to function at the level of the effector caspases, expression of a cytosolic Smac/DIABLO in Type II cells allowed TRAIL to bypass Bcl-xL inhibition of death receptor-induced apoptosis. Combined, these data suggest that Smac/DIABLO plays a critical role in neutralizing IAP inhibition of the effector caspases in the death receptor pathway of Type II cells.
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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/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/BCL2L1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Bacterial Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/DIABLO protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Inhibitor of Apoptosis Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Insect Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Mitochondrial Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor,
http://linkedlifedata.com/resource/pubmed/chemical/TNF-Related Apoptosis-Inducing...,
http://linkedlifedata.com/resource/pubmed/chemical/TNFSF10 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/X-Linked Inhibitor of Apoptosis...,
http://linkedlifedata.com/resource/pubmed/chemical/XIAP protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-X Protein
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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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 |
17
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pubmed:volume |
275
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
36152-7
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pubmed:dateRevised |
2008-5-14
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pubmed:meshHeading |
pubmed-meshheading:10950947-Amino Acid Sequence,
pubmed-meshheading:10950947-Apoptosis,
pubmed-meshheading:10950947-Apoptosis Regulatory Proteins,
pubmed-meshheading:10950947-Bacterial Proteins,
pubmed-meshheading:10950947-Carrier Proteins,
pubmed-meshheading:10950947-Caspases,
pubmed-meshheading:10950947-Cell Differentiation,
pubmed-meshheading:10950947-Cytosol,
pubmed-meshheading:10950947-Enzyme Activation,
pubmed-meshheading:10950947-Humans,
pubmed-meshheading:10950947-Inhibitor of Apoptosis Proteins,
pubmed-meshheading:10950947-Insect Proteins,
pubmed-meshheading:10950947-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:10950947-Membrane Glycoproteins,
pubmed-meshheading:10950947-Mitochondria,
pubmed-meshheading:10950947-Mitochondrial Proteins,
pubmed-meshheading:10950947-Molecular Sequence Data,
pubmed-meshheading:10950947-Mutation,
pubmed-meshheading:10950947-Protein Binding,
pubmed-meshheading:10950947-Protein Isoforms,
pubmed-meshheading:10950947-Proteins,
pubmed-meshheading:10950947-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:10950947-Receptors, Tumor Necrosis Factor,
pubmed-meshheading:10950947-Signal Transduction,
pubmed-meshheading:10950947-TNF-Related Apoptosis-Inducing Ligand,
pubmed-meshheading:10950947-Transfection,
pubmed-meshheading:10950947-Tumor Cells, Cultured,
pubmed-meshheading:10950947-Tumor Necrosis Factor-alpha,
pubmed-meshheading:10950947-X-Linked Inhibitor of Apoptosis Protein,
pubmed-meshheading:10950947-bcl-X Protein
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pubmed:year |
2000
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pubmed:articleTitle |
Molecular determinants of the caspase-promoting activity of Smac/DIABLO and its role in the death receptor pathway.
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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.
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