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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
32
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pubmed:dateCreated |
2003-8-4
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pubmed:abstractText |
Induction and execution of apoptosis programs are generally believed to be mediated through a hierarchy of caspase activation. By using two cellular variants obtained from the L1210 cell line (L1210/S and L1210/0), we have shown previously that staurosporine induces apoptotic cell death through both caspase-dependent and caspase-independent pathways. Both pathways normally coexisted in L1210/S cells, whereas L1210/0 cells lacked the ability to activate caspases despite the confirmed presence of both procaspase-3 and -9. Here we show that this defect in caspase activation is not due to mechanisms such as an absence of cytochrome c release, the expression of non-functional caspases, or the presence of an endogenous inhibitor but results from the loss of apoptosis protease activator protein-1 (APAF-1) expression. This absence of APAF-1 protein results from multiple alterations at both genomic and transcriptional levels. However, although this lack of APAF-1 delays the apoptotic program, it does not hamper its execution. Importantly, in these cells, apoptosis develops not only in an APAF-1-independent way but also in the absence of caspase-3 and -9 activation. Altogether these findings provide evidence that apoptosis may occur through alternative signaling pathways independent of APAF-1 expression and totally dissociated from any caspase processing. Therefore, the L1210/0 variant sub-line provides a valuable tool for the elucidation of these pathways.
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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/Apaf1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Apoptotic Protease-Activating...,
http://linkedlifedata.com/resource/pubmed/chemical/Casp3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Casp9 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome c Group,
http://linkedlifedata.com/resource/pubmed/chemical/Granzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Gzmb protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Serine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Staurosporine
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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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 |
8
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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 |
29571-80
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:12773531-Animals,
pubmed-meshheading:12773531-Apoptosis,
pubmed-meshheading:12773531-Apoptotic Protease-Activating Factor 1,
pubmed-meshheading:12773531-Blotting, Southern,
pubmed-meshheading:12773531-Blotting, Western,
pubmed-meshheading:12773531-Caspase 3,
pubmed-meshheading:12773531-Caspase 9,
pubmed-meshheading:12773531-Caspases,
pubmed-meshheading:12773531-Cell Line,
pubmed-meshheading:12773531-Cell Survival,
pubmed-meshheading:12773531-Cell-Free System,
pubmed-meshheading:12773531-Cytochrome c Group,
pubmed-meshheading:12773531-Enzyme Activation,
pubmed-meshheading:12773531-Exons,
pubmed-meshheading:12773531-Flow Cytometry,
pubmed-meshheading:12773531-Gene Deletion,
pubmed-meshheading:12773531-Granzymes,
pubmed-meshheading:12773531-Membrane Potentials,
pubmed-meshheading:12773531-Mice,
pubmed-meshheading:12773531-Mitochondria,
pubmed-meshheading:12773531-Models, Genetic,
pubmed-meshheading:12773531-Proteins,
pubmed-meshheading:12773531-RNA, Messenger,
pubmed-meshheading:12773531-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:12773531-Serine Endopeptidases,
pubmed-meshheading:12773531-Signal Transduction,
pubmed-meshheading:12773531-Staurosporine,
pubmed-meshheading:12773531-Time Factors,
pubmed-meshheading:12773531-Tumor Cells, Cultured
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pubmed:year |
2003
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pubmed:articleTitle |
Apoptosome-independent pathway for apoptosis. Biochemical analysis of APAF-1 defects and biological outcomes.
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pubmed:affiliation |
INSERM U496, Centre G. Hayem, Hôpital Saint-Louis, 1, Avenue Claude Vellefaux, 75010 Paris, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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