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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
2005-3-14
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pubmed:abstractText |
Molecular hardwiring of the cell cycle to the apoptotic machinery is a critical tumor suppressor mechanism for eliminating hyperproliferative cells. Deregulation of the Rb-E2F repressor complex by genetic deletion or functional inhibition of Rb triggers apoptosis through both the intrinsic (caspase-9 mediated) and extrinsic (caspase-8 mediated) death pathways. Induction of the intrinsic pathway has been studied extensively and involves release of free E2F and direct transcriptional activation of E2F-responsive apoptotic genes such as ARF, APAF1, and CASP9. In contrast, the mechanisms leading to activation of the extrinsic pathway are less well understood. There is growing evidence that Rb-E2F perturbation induces the extrinsic pathway, at least in part, through derepression (as opposed to transactivation) of apoptotic genes. Here, we explore this possibility using cells in which Rb-E2F complexes are displaced from promoters without stimulating E2F transactivation. This derepression of Rb-E2F-regulated genes leads to apoptosis through inactivation of focal adhesion kinase and activation of caspase-8. These findings reveal a new mechanistic link between Rb-E2F and the extrinsic (caspase 8-mediated) 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/ADP-Ribosylation Factors,
http://linkedlifedata.com/resource/pubmed/chemical/APAF1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Apaf1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Apoptotic Protease-Activating...,
http://linkedlifedata.com/resource/pubmed/chemical/CASP8 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CASP9 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Casp8 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Casp9 protein, rat,
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/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/E2F Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Focal Adhesion Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Focal Adhesion Protein-Tyrosine...,
http://linkedlifedata.com/resource/pubmed/chemical/PTK2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ptk2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Retinoblastoma Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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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 |
18
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pubmed:volume |
280
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
10484-90
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15640164-ADP-Ribosylation Factors,
pubmed-meshheading:15640164-Animals,
pubmed-meshheading:15640164-Apoptosis,
pubmed-meshheading:15640164-Apoptotic Protease-Activating Factor 1,
pubmed-meshheading:15640164-Caspase 8,
pubmed-meshheading:15640164-Caspase 9,
pubmed-meshheading:15640164-Caspases,
pubmed-meshheading:15640164-Cell Cycle,
pubmed-meshheading:15640164-Cell Cycle Proteins,
pubmed-meshheading:15640164-Cell Line,
pubmed-meshheading:15640164-Cell Line, Tumor,
pubmed-meshheading:15640164-Cell Proliferation,
pubmed-meshheading:15640164-Cell Separation,
pubmed-meshheading:15640164-Cell Survival,
pubmed-meshheading:15640164-DNA, Complementary,
pubmed-meshheading:15640164-DNA-Binding Proteins,
pubmed-meshheading:15640164-E2F Transcription Factors,
pubmed-meshheading:15640164-Enzyme Inhibitors,
pubmed-meshheading:15640164-Fibroblasts,
pubmed-meshheading:15640164-Flow Cytometry,
pubmed-meshheading:15640164-Focal Adhesion Kinase 1,
pubmed-meshheading:15640164-Focal Adhesion Protein-Tyrosine Kinases,
pubmed-meshheading:15640164-Humans,
pubmed-meshheading:15640164-Models, Biological,
pubmed-meshheading:15640164-Mutation,
pubmed-meshheading:15640164-Phosphorylation,
pubmed-meshheading:15640164-Plasmids,
pubmed-meshheading:15640164-Polymerase Chain Reaction,
pubmed-meshheading:15640164-Protein Binding,
pubmed-meshheading:15640164-Protein Structure, Tertiary,
pubmed-meshheading:15640164-Protein-Tyrosine Kinases,
pubmed-meshheading:15640164-Proteins,
pubmed-meshheading:15640164-RNA, Messenger,
pubmed-meshheading:15640164-RNA, Small Interfering,
pubmed-meshheading:15640164-Rats,
pubmed-meshheading:15640164-Retinoblastoma Protein,
pubmed-meshheading:15640164-Time Factors,
pubmed-meshheading:15640164-Transcription, Genetic,
pubmed-meshheading:15640164-Transcription Factors,
pubmed-meshheading:15640164-Transcriptional Activation,
pubmed-meshheading:15640164-Up-Regulation
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pubmed:year |
2005
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pubmed:articleTitle |
Loss of Rb-E2F repression results in caspase-8-mediated apoptosis through inactivation of focal adhesion kinase.
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pubmed:affiliation |
Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, 660 South Euclid Ave, St. Louis, Missouri 63110, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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