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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
29
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pubmed:dateCreated |
2008-7-3
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pubmed:abstractText |
We previously reported that actin damage by treatment with an actin-depolymerizing agent including pectenotoxin-2 induces Bim-mediated apoptosis in p53-deficient human tumors. In this study, we investigated a molecular mechanism underlying Bim-mediated apoptosis of p53-deficient tumor cells following actin damage. We found that actin inhibitors increased the protein levels of p53 and p21 and thereby inactivated both Cdk2 and Cdc2 kinases. However, p53- or p21-knockout cells fail to induce p21 and hence kept both Cdk2 and Cdc2 kinases active even after treatment with actin inhibitor. The p53- or p21-knockout cells became multinucleate and polyploidy in association with induction of apoptosis. Expression of Bcl-x(L) resulted in accumulation of polyploid cells in association with inhibition of apoptosis. However, expression of a dominant negative mutant (Cdk2dn) and treatment with chemical inhibitors for Cdk2 suppressed not only accumulation of multinucleated cells, but also induction of Bim expression and apoptosis. Therefore, these results suggest that Bim-mediated apoptosis following actin damage due to deregulation of Cdk2 and the cell cycle by the absence of functional p53.
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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/Actins,
http://linkedlifedata.com/resource/pubmed/chemical/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/BCL2L1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Bcl-2-like protein 11,
http://linkedlifedata.com/resource/pubmed/chemical/CDC2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CDK2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin B,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Furans,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrans,
http://linkedlifedata.com/resource/pubmed/chemical/TP53 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-X Protein,
http://linkedlifedata.com/resource/pubmed/chemical/pectenotoxin 2
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1476-5594
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
3
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pubmed:volume |
27
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4115-21
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:18345036-Actins,
pubmed-meshheading:18345036-Apoptosis,
pubmed-meshheading:18345036-Apoptosis Regulatory Proteins,
pubmed-meshheading:18345036-Cell Line, Tumor,
pubmed-meshheading:18345036-Colorectal Neoplasms,
pubmed-meshheading:18345036-Cyclin B,
pubmed-meshheading:18345036-Cyclin-Dependent Kinase 2,
pubmed-meshheading:18345036-Furans,
pubmed-meshheading:18345036-Gene Expression,
pubmed-meshheading:18345036-Genes, Dominant,
pubmed-meshheading:18345036-Humans,
pubmed-meshheading:18345036-Membrane Proteins,
pubmed-meshheading:18345036-Mutation,
pubmed-meshheading:18345036-Polyploidy,
pubmed-meshheading:18345036-Proto-Oncogene Proteins,
pubmed-meshheading:18345036-Pyrans,
pubmed-meshheading:18345036-Tumor Suppressor Protein p53,
pubmed-meshheading:18345036-bcl-X Protein
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pubmed:year |
2008
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pubmed:articleTitle |
Deregulation of Cdk2 causes Bim-mediated apoptosis in p53-deficient tumors following actin damage.
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pubmed:affiliation |
National Research Laboratory, Department of Microbiology, Dankook University College of Medicine, Cheonan, Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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