Source:http://linkedlifedata.com/resource/pubmed/id/16579975
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
11
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pubmed:dateCreated |
2006-5-1
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pubmed:abstractText |
It is known that by binding to the FAS-associated death domain (FADD) protein and/or caspases-8 and -10 at the level of the death-inducing signaling complex (DISC), cellular FLICE-like inhibitory protein (c-FLIP) can prevent apoptosis triggered by death-inducing ligands. We investigated whether the c-FLIP splice variants, c-FLIP long [c-FLIP(L)] and c-FLIP short [c-FLIP(S)], play a role in Taxol-induced apoptosis. Our results showed that low Taxol concentrations triggered caspase-8- and caspase-10-dependent apoptosis in the CCRF-HSB-2 human lymphoblastic leukemia cell line, and induced the down-regulation of c-FLIP(S) and c-FLIP(L). Taxol decreased the expression of c-FLIP by a post-transcriptional and caspase-independent mechanism. To explore the distinct functions of the c-FLIP variants in Taxol-induced apoptosis, we transfected the cells with expression vectors carrying c-FLIP(L) and c-FLIP(S) in the sense orientation or c-FLIP(S) in the antisense orientation [c-FLIP(S)-AS]. Caspases-8 and -10 were more efficiently activated in the c-FLIP(S)-AS strain treated with 5-50nM Taxol, which revealed that c-FLIP regulates Taxol-induced apoptosis by interacting with these caspases. Furthermore, our data showed that increased expression of c-FLIP(L) or c-FLIP(S) reduced apoptosis at 5-50nM Taxol concentrations suggesting that both isoforms of c-FLIP prevent Taxol-induced apoptosis. These results revealed that Taxol induces apoptosis by down-regulating c-FLIP(S) and c-FLIP(L) expression.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Phytogenic,
http://linkedlifedata.com/resource/pubmed/chemical/CASP10 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CASP8 and FADD-Like Apoptosis...,
http://linkedlifedata.com/resource/pubmed/chemical/CASP8 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CFLAR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 10,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 8,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Paclitaxel
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0006-2952
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
28
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pubmed:volume |
71
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1551-61
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:16579975-Antineoplastic Agents, Phytogenic,
pubmed-meshheading:16579975-Apoptosis,
pubmed-meshheading:16579975-CASP8 and FADD-Like Apoptosis Regulating Protein,
pubmed-meshheading:16579975-Caspase 10,
pubmed-meshheading:16579975-Caspase 8,
pubmed-meshheading:16579975-Caspases,
pubmed-meshheading:16579975-Cell Line, Tumor,
pubmed-meshheading:16579975-Dose-Response Relationship, Drug,
pubmed-meshheading:16579975-Down-Regulation,
pubmed-meshheading:16579975-Humans,
pubmed-meshheading:16579975-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:16579975-Leukemia-Lymphoma, Adult T-Cell,
pubmed-meshheading:16579975-Paclitaxel
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pubmed:year |
2006
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pubmed:articleTitle |
Cellular FLICE-like inhibitory protein (c-FLIP): a novel target for Taxol-induced apoptosis.
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pubmed:affiliation |
Department of Pharmacology and Toxicology, Indiana University Cancer Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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