Induction of cyclin E-cdk2 kinase activity, E2F-dependent transcription and cell growth by Myc are genetically separable events.

Publication Type:

Journal Article

Source:

The EMBO journal, Volume 19, Issue 21, p.5813-23 (2000)

Keywords:

3T3 Cells, Animals, APOPTOSIS, Carrier Proteins, CDC2-CDC28 Kinases, Cell Cycle Proteins, Cell Division, Cells, Cultured, Cyclin E, Cyclin-Dependent Kinase 2, Cyclin-Dependent Kinase Inhibitor p27, Cyclin-Dependent Kinases, DNA-Binding Proteins, E2F Transcription Factors, Enzyme Induction, Genes, myc, MICE, Mice, Knockout, Microtubule-Associated Proteins, Protein-Serine-Threonine Kinases, Retinoblastoma-Binding Protein 1, Retroviridae, Transcription Factor DP1, TRANSCRIPTION FACTORS, Transcription, Genetic, Transfection, Tumor Suppressor Proteins

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.