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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
21
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pubmed:dateCreated |
1998-12-22
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pubmed:abstractText |
Expression of the B-Myb transcription factor is upregulated during late G1 phase of the cell cycle by an E2F-dependent transcriptional mechanism. B-Myb is specifically phosphorylated during S phase, suggesting that a cyclin-dependent kinase (Cdk) regulates its activity. Consistent with this notion, the S phase-specific cyclin A/Cdk2 was found previously to enhance B-Myb transactivation activity in cotransfected cells. In this study we provide evidence that B-Myb is a direct physiological target for cyclin A/Cdk2. We demonstrate that B-Myb is an in vitro substrate for cyclin A/Cdk2, but not for cyclin D1/Cdk4 or cyclin E/Cdk2. By mutating candidate Cdk2 phosphorylation sites, we show that B-Myb is phosphorylated at Thr447, Thr490, Thr497 and Ser581 by cyclin A/Cdk2 in vitro and that these sites are also phosphorylated in cycling U-2 OS cells. Inhibition of endogenous Cdk2 by dominant negative Cdk2 attenuated phosphorylation of Thr447, Thr490 and Thr497, but had no effect upon Ser581 modification. B-Myb transactivation activity was significantly reduced in a mutant containing amino acid substitutions at all four identified cyclin A/Cdk2 sites and was constitutively low in Saos-2 cells where endogenous cyclin A/Cdk2 activity was unable to phosphorylate ectopically expressed B-Myb. These data indicate that phosphorylation by cyclin A/Cdk2 is directly involved in enhancing B-Myb transactivation activity and that levels of endogenous cyclin A/Cdk2 activity may contribute to cell line-specific B-Myb function.
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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/CDC2-CDC28 Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/CDK2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin A,
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/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/MYBL2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoserine,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphothreonine,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0950-9232
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
26
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pubmed:volume |
17
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2679-89
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:9840932-Bone Neoplasms,
pubmed-meshheading:9840932-CDC2-CDC28 Kinases,
pubmed-meshheading:9840932-Cell Cycle Proteins,
pubmed-meshheading:9840932-Cyclin A,
pubmed-meshheading:9840932-Cyclin-Dependent Kinase 2,
pubmed-meshheading:9840932-Cyclin-Dependent Kinases,
pubmed-meshheading:9840932-DNA-Binding Proteins,
pubmed-meshheading:9840932-G1 Phase,
pubmed-meshheading:9840932-Gene Expression Regulation,
pubmed-meshheading:9840932-Humans,
pubmed-meshheading:9840932-Osteosarcoma,
pubmed-meshheading:9840932-Phosphorylation,
pubmed-meshheading:9840932-Phosphoserine,
pubmed-meshheading:9840932-Phosphothreonine,
pubmed-meshheading:9840932-Protein Processing, Post-Translational,
pubmed-meshheading:9840932-Protein-Serine-Threonine Kinases,
pubmed-meshheading:9840932-Recombinant Fusion Proteins,
pubmed-meshheading:9840932-S Phase,
pubmed-meshheading:9840932-Structure-Activity Relationship,
pubmed-meshheading:9840932-Substrate Specificity,
pubmed-meshheading:9840932-Trans-Activators,
pubmed-meshheading:9840932-Transcriptional Activation,
pubmed-meshheading:9840932-Transfection,
pubmed-meshheading:9840932-Tumor Cells, Cultured
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pubmed:year |
1998
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pubmed:articleTitle |
The cell-cycle regulated transcription factor B-Myb is phosphorylated by cyclin A/Cdk2 at sites that enhance its transactivation properties.
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pubmed:affiliation |
Section of Virology and Cell Biology and Ludwig Institute for Cancer Research, Imperial College School of Medicine, St Mary's Campus, London, UK.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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