Source:http://linkedlifedata.com/resource/pubmed/id/12801928
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
34
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pubmed:dateCreated |
2003-8-18
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pubmed:abstractText |
Cdc25A regulates cell cycle progression, has oncogenic and anti-apoptotic activity, and is over-expressed in many human tumors. Phosphorylation by Chk1 and Cds1/Chk2 down-regulates Cdc25A levels in response to genotoxic stresses. Nevertheless, it remains unclear whether Chk1 and Cds1/Chk2 are uniquely responsible for regulating Cdc25A stability during interphase or if other kinase activities contribute. Here we report that treatment of HeLa cells with the cyclin-dependent kinase inhibitor roscovitine caused a concentration- and time-dependent increase in Cdc25A protein levels. Transfection with dominant-negative Cdk mutants demonstrated that only a Cdk2 mutant increased Cdc25A protein levels; Cdk1 and Cdk3 mutants had no effect. The increased Cdc25A protein levels were the result of an increase in the half-life of the protein; no increase in Cdc25A mRNA levels was observed. These results demonstrate Cdk2 kinase activity contributes to the labile nature of Cdc25A during interphase and redefine the nature of the Cdc25A-Cdk2 autoamplification feedback loop.
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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/CDC2-CDC28 Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/CDC25A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CDK2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/cdc25 Phosphatases
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
22
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
31838-42
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12801928-CDC2-CDC28 Kinases,
pubmed-meshheading:12801928-Cyclin-Dependent Kinase 2,
pubmed-meshheading:12801928-Cyclin-Dependent Kinases,
pubmed-meshheading:12801928-Half-Life,
pubmed-meshheading:12801928-Humans,
pubmed-meshheading:12801928-Interphase,
pubmed-meshheading:12801928-Phosphorylation,
pubmed-meshheading:12801928-Protein-Serine-Threonine Kinases,
pubmed-meshheading:12801928-Tumor Cells, Cultured,
pubmed-meshheading:12801928-cdc25 Phosphatases
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pubmed:year |
2003
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pubmed:articleTitle |
Regulation of Cdc25A half-life in interphase by cyclin-dependent kinase 2 activity.
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pubmed:affiliation |
Department of Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, 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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