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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
42
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pubmed:dateCreated |
2002-10-15
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pubmed:abstractText |
We have previously shown that cyclin E can malignantly transform primary rat embryo fibroblasts in cooperation with constitutively active Ha-Ras. In addition, we demonstrated that high level cyclin E expression potentiates the development of methyl-nitroso-urea-induced T-cell lymphomas in mice. To further investigate the mechanism underlying cyclin E-mediated malignant transformation, we have performed a mutational analysis of cyclin E function. Here we show that cyclin E mutants defective to form an active kinase complex with Cdk2 are unable to drive cells from G(1) into S phase but can still malignantly transform rat embryo fibroblasts in cooperation with Ha-Ras. In addition, Cdk2 activation is not a prerequisite for the ability of cyclin E to rescue yeast triple cln mutations. We also find that the oncogenic properties of cyclin E did not entirely correspond with its ability to interact with the negative cell cycle regulator p27(Kip1) or the pocket protein p130. These findings suggest that the oncogenic activity of cyclin E does not exclusively rely on its ability as a positive regulator of G(1) progression. Rather, we propose that cyclin E harbors other functions, independent of Cdk2 activation and p27(Kip1) binding, that contribute significantly to its oncogenic activity.
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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/Blood Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/CDC2-CDC28 Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/CDK2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cdk2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cdk2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Cdkn1b protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cdkn1b protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin E,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RBL2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Rbl2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Rbl2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Retinoblastoma-Like Protein p130,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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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 |
277
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
39909-18
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12149264-3T3 Cells,
pubmed-meshheading:12149264-Animals,
pubmed-meshheading:12149264-Blood Proteins,
pubmed-meshheading:12149264-Blotting, Western,
pubmed-meshheading:12149264-CDC2-CDC28 Kinases,
pubmed-meshheading:12149264-Cell Cycle Proteins,
pubmed-meshheading:12149264-Cyclin E,
pubmed-meshheading:12149264-Cyclin-Dependent Kinase 2,
pubmed-meshheading:12149264-Cyclin-Dependent Kinase Inhibitor p27,
pubmed-meshheading:12149264-Cyclin-Dependent Kinases,
pubmed-meshheading:12149264-DNA, Complementary,
pubmed-meshheading:12149264-Enzyme Activation,
pubmed-meshheading:12149264-Fibroblasts,
pubmed-meshheading:12149264-G1 Phase,
pubmed-meshheading:12149264-Humans,
pubmed-meshheading:12149264-Mice,
pubmed-meshheading:12149264-Mutation,
pubmed-meshheading:12149264-Plasmids,
pubmed-meshheading:12149264-Precipitin Tests,
pubmed-meshheading:12149264-Protein Binding,
pubmed-meshheading:12149264-Protein-Serine-Threonine Kinases,
pubmed-meshheading:12149264-Proteins,
pubmed-meshheading:12149264-Rats,
pubmed-meshheading:12149264-Rats, Inbred F344,
pubmed-meshheading:12149264-Retinoblastoma-Like Protein p130,
pubmed-meshheading:12149264-S Phase,
pubmed-meshheading:12149264-Tumor Suppressor Proteins,
pubmed-meshheading:12149264-Two-Hybrid System Techniques
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pubmed:year |
2002
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pubmed:articleTitle |
The oncogenic activity of cyclin E is not confined to Cdk2 activation alone but relies on several other, distinct functions of the protein.
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pubmed:affiliation |
Institut für Zellbiologie (Tumorforschung), IFZ, Universitätsklinikum Essen, Virchowstrasse 173, D-45122 Essen, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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