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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2004-1-5
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pubmed:abstractText |
FLICE-inhibitory protein (FLIP) is a homolog of caspase-8 that lacks catalytic activity and has been shown to be important in protecting endothelial cells from apoptosis. The serine/threonine kinase Akt/PKB was recently reported to promote FLIP expression in endothelial and tumor cells. Here we examined the role of the forkhead transcription factor FOXO3a, a downstream target of Akt, in controlling FLIP regulation in endothelial cells. FOXO3a nuclear translocation was regulated by Akt in human umbilical vein endothelial cells. Transduction of a nonphosphorylatable, constitutively active mutant of FOXO3a (TM-FOXO3a) led to the down-regulation of FLIP levels. Transduction with TM-FOXO3a also increased caspase-8 activity and promoted apoptosis in endothelial cells. Conversely, transduction of a dominant-negative mutant of FOXO3a up-regulated FLIP levels and protected endothelial cells from apoptosis under serum deprivation conditions. Restoration of intracellular FLIP blocked caspase-8 activation and inhibited apoptosis in TM-FOXO3a-transduced cells. These data suggest that FOXO3a is a downstream target of Akt in endothelial cells that can promote apoptosis via FLIP down-regulation and activation of the extrinsic apoptotic pathway.
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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/AKT1 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/CASP9 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CFLAR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
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/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/FOXO1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Forkhead Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Growth Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Luminescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/RNA,
http://linkedlifedata.com/resource/pubmed/chemical/Ribonucleases,
http://linkedlifedata.com/resource/pubmed/chemical/Serpins,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Viral Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/interleukin-1beta-converting...
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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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 |
9
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1513-25
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:14551207-Humans,
pubmed-meshheading:14551207-Umbilical Veins,
pubmed-meshheading:14551207-Mutation,
pubmed-meshheading:14551207-Ribonucleases,
pubmed-meshheading:14551207-Microscopy, Fluorescence,
pubmed-meshheading:14551207-Enzyme Inhibitors,
pubmed-meshheading:14551207-RNA,
pubmed-meshheading:14551207-Growth Substances,
pubmed-meshheading:14551207-Time Factors,
pubmed-meshheading:14551207-Cells, Cultured,
pubmed-meshheading:14551207-Viral Proteins,
pubmed-meshheading:14551207-Endothelium, Vascular,
pubmed-meshheading:14551207-Models, Biological,
pubmed-meshheading:14551207-Cell Survival,
pubmed-meshheading:14551207-Enzyme Activation,
pubmed-meshheading:14551207-Cell Separation,
pubmed-meshheading:14551207-Carrier Proteins,
pubmed-meshheading:14551207-Protein Structure, Tertiary,
pubmed-meshheading:14551207-DNA Fragmentation,
pubmed-meshheading:14551207-Signal Transduction,
pubmed-meshheading:14551207-DNA-Binding Proteins,
pubmed-meshheading:14551207-Down-Regulation,
pubmed-meshheading:14551207-Apoptosis,
pubmed-meshheading:14551207-Transcription Factors,
pubmed-meshheading:14551207-Endothelial Cells,
pubmed-meshheading:14551207-Luminescent Proteins,
pubmed-meshheading:14551207-Flow Cytometry,
pubmed-meshheading:14551207-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:14551207-Protein-Serine-Threonine Kinases,
pubmed-meshheading:14551207-Serpins,
pubmed-meshheading:14551207-Active Transport, Cell Nucleus,
pubmed-meshheading:14551207-Blotting, Western,
pubmed-meshheading:14551207-Up-Regulation,
pubmed-meshheading:14551207-Proto-Oncogene Proteins,
pubmed-meshheading:14551207-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:14551207-Forkhead Transcription Factors
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