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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
41
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pubmed:dateCreated |
2000-11-13
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pubmed:abstractText |
The IAP (inhibitor of apoptosis) family of anti-apoptotic proteins regulates programmed cell death. Of the six known human IAP-related proteins, XIAP is the most potent inhibitor. To study the mechanistic effects of XIAP on DNA damage-induced apoptosis, we prepared U-937 cells that stably overexpress XIAP. The results demonstrate that XIAP inhibits apoptosis induced by 1-[beta-d-arabinofuranosyl]cytosine (ara-C) and other genotoxic agents. XIAP had no detectable effect on ara-C-induced release of mitochondrial cytochrome c and attenuated cleavage of procaspase-9. In addition, we show that ara-C induces the association of XIAP with the cleaved fragments of caspase-9 and thereby inhibition of caspase-9 activity. The results also demonstrate that ara-C induces cleavage of procaspase-3 by a caspase-8-dependent mechanism and that XIAP inhibits caspase-3 activity. These results demonstrate that XIAP functions downstream of procaspase-9 cleavage as an inhibitor of both proteolytically processed caspase-9 and -3 in the cellular response to genotoxic stress.
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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/CASP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CASP8 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CASP9 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 8,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Cytarabine,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome c Group,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/Mutagens,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/X-Linked Inhibitor of Apoptosis...,
http://linkedlifedata.com/resource/pubmed/chemical/XIAP protein, human
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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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 |
13
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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 |
31733-8
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pubmed:dateRevised |
2008-5-14
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pubmed:meshHeading |
pubmed-meshheading:10930419-Apoptosis,
pubmed-meshheading:10930419-Caspase 3,
pubmed-meshheading:10930419-Caspase 8,
pubmed-meshheading:10930419-Caspase 9,
pubmed-meshheading:10930419-Caspases,
pubmed-meshheading:10930419-Cytarabine,
pubmed-meshheading:10930419-Cytochrome c Group,
pubmed-meshheading:10930419-DNA Damage,
pubmed-meshheading:10930419-DNA Fragmentation,
pubmed-meshheading:10930419-Enzyme Activation,
pubmed-meshheading:10930419-Enzyme Precursors,
pubmed-meshheading:10930419-Humans,
pubmed-meshheading:10930419-Mitochondria,
pubmed-meshheading:10930419-Models, Biological,
pubmed-meshheading:10930419-Mutagens,
pubmed-meshheading:10930419-Peptide Fragments,
pubmed-meshheading:10930419-Precipitin Tests,
pubmed-meshheading:10930419-Protein Binding,
pubmed-meshheading:10930419-Protein Processing, Post-Translational,
pubmed-meshheading:10930419-Proteins,
pubmed-meshheading:10930419-Transfection,
pubmed-meshheading:10930419-U937 Cells,
pubmed-meshheading:10930419-X-Linked Inhibitor of Apoptosis Protein
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pubmed:year |
2000
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pubmed:articleTitle |
XIAP regulates DNA damage-induced apoptosis downstream of caspase-9 cleavage.
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pubmed:affiliation |
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. Rakesh_Datta@dfci.harvard.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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