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

The c-myc gene has been implicated in three distinct genetic programs regul ating cell proliferation: control of cyclin E-cdk2 kinase activity, E2F-dep endent transcription and cell growth. We have now used p27(-/-) fibroblasts to dissect these downstream signalling pathways. In these cells, activatio n of Myc stimulates transcription of E2F target genes, S-phase entry and ce ll growth without affecting cyclin E-cdk2 kinase activity. Both cyclin D2 a nd E2F2, potential direct target genes of Myc, are induced in p27(-/-) MycE R dells. 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 transcript ion and of cell growth by Myc can be genetically separated from each other.