Abstract
The c-myc gene has been implicated in three distinct genetic programs regulating cell proliferation: control of cyclin E-cdk2 kinase activity, E2F-dependent transcription and cell growth. We have now used p27(-/-) fibroblasts to dissect these downstream signalling pathways. In these cells, activation of Myc stimulates transcription of E2F target genes, S-phase entry and cell growth without affecting cyclin E-cdk2 kinase activity. Both cyclin D2 and E2F2, potential direct target genes of Myc, are induced in p27(-/-) MycER cells. Ectopic expression of E2F2, but not of cyclin D2, induces S-phase entry, but, in contrast to Myc, does not stimulate cell growth. Our results show that stimulation of cyclin E-cdk2 kinase, of E2F-dependent transcription and of cell growth by Myc can be genetically separated from each other.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Animals
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Apoptosis
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CDC2-CDC28 Kinases*
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Carrier Proteins*
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Cell Cycle Proteins*
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Cell Division
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Cells, Cultured
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Cyclin E / metabolism*
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinase Inhibitor p27
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Cyclin-Dependent Kinases / biosynthesis*
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DNA-Binding Proteins*
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E2F Transcription Factors
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Enzyme Induction
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Genes, myc*
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Mice
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Mice, Knockout
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Microtubule-Associated Proteins / genetics
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Microtubule-Associated Proteins / metabolism
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Protein Serine-Threonine Kinases / biosynthesis*
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Retinoblastoma-Binding Protein 1
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Retroviridae / genetics
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Transcription Factor DP1
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Transcription Factors / metabolism*
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Transcription, Genetic
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Transfection
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Tumor Suppressor Proteins*
Substances
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Arid4a protein, mouse
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Carrier Proteins
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Cdkn1b protein, mouse
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Cell Cycle Proteins
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Cyclin E
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DNA-Binding Proteins
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E2F Transcription Factors
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Microtubule-Associated Proteins
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Retinoblastoma-Binding Protein 1
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Transcription Factor DP1
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Transcription Factors
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Tumor Suppressor Proteins
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Cyclin-Dependent Kinase Inhibitor p27
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Protein Serine-Threonine Kinases
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CDC2-CDC28 Kinases
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Cdk2 protein, mouse
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinases