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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 |
2005-2-15
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pubmed:abstractText |
Pten-/- cells display a partially defective checkpoint in response to ionizing radiation (IR). The checkpoint defect was traced to the ability of AKT to phosphorylate CHK1 at serine 280, since a nonphosphorylated mutant of CHK1 (S280A) complemented the checkpoint defect and restored CDC25A degradation. CHK1 phosphorylation at serine 280 led to covalent binding of 1 to 2 molecules of ubiquitin and cytoplasmic CHK1 localization. Primary breast carcinomas lacking PTEN expression and having elevated AKT phosphorylation had increased cytoplasmic CHK1 and displayed aneuploidy (p <0.005). We conclude that loss of PTEN and subsequent activation of AKT impair CHK1 through phosphorylation, ubiquitination, and reduced nuclear localization to promote genomic instability in tumor cells.
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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/Checkpoint kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Growth Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoric Monoester Hydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
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/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1535-6108
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pubmed:author |
pubmed-author:ChoudhuryAtish DAD,
pubmed-author:GaciongZbigniewZ,
pubmed-author:HibshooshHaninaH,
pubmed-author:KeniryMeganM,
pubmed-author:LiHong ShenHS,
pubmed-author:MansukhaniMaheshM,
pubmed-author:MeekSarah E MSE,
pubmed-author:MemeoLorenzoL,
pubmed-author:MurtyVundavalli V V SVV,
pubmed-author:PanditaTej KTK,
pubmed-author:ParsonsRamonR,
pubmed-author:Piwnica-WormsHelenH,
pubmed-author:PucJanuszJ
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pubmed:issnType |
Print
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pubmed:volume |
7
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
193-204
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:15710331-Animals,
pubmed-meshheading:15710331-Breast Neoplasms,
pubmed-meshheading:15710331-Cell Line,
pubmed-meshheading:15710331-Cell Line, Tumor,
pubmed-meshheading:15710331-Cytoplasm,
pubmed-meshheading:15710331-DNA Damage,
pubmed-meshheading:15710331-Embryo, Mammalian,
pubmed-meshheading:15710331-G2 Phase,
pubmed-meshheading:15710331-Growth Substances,
pubmed-meshheading:15710331-Humans,
pubmed-meshheading:15710331-Mice,
pubmed-meshheading:15710331-Mice, Knockout,
pubmed-meshheading:15710331-Mice, Transgenic,
pubmed-meshheading:15710331-Models, Biological,
pubmed-meshheading:15710331-Models, Genetic,
pubmed-meshheading:15710331-Mutation,
pubmed-meshheading:15710331-Phosphoric Monoester Hydrolases,
pubmed-meshheading:15710331-Phosphorylation,
pubmed-meshheading:15710331-Plasmids,
pubmed-meshheading:15710331-Protein Kinases,
pubmed-meshheading:15710331-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15710331-Proto-Oncogene Proteins,
pubmed-meshheading:15710331-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:15710331-Radiation, Ionizing,
pubmed-meshheading:15710331-Serine,
pubmed-meshheading:15710331-Signal Transduction,
pubmed-meshheading:15710331-Stem Cells,
pubmed-meshheading:15710331-Time Factors,
pubmed-meshheading:15710331-Ubiquitin
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pubmed:year |
2005
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pubmed:articleTitle |
Lack of PTEN sequesters CHK1 and initiates genetic instability.
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pubmed:affiliation |
Institute for Cancer Genetics, Columbia University, New York, New York 10032, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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