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  • The EMBO Journal (2000) 19, 5813 - 5823
  • doi:10.1093/emboj/19.21.5813

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

Rudolf Beier1, Andrea Bürgin1, Astrid Kiermaier1, Matthew Fero2, Holger Karsunky3, Rainer Saffrich4, Tarik Möröy3, Wilhelm Ansorge4, Jim Roberts2 and Martin Eilers1

  1. Institute of Molecular Biology and Tumour Research, Emil-Mannkopff-Stras zlige 2, 35033 Marburg, Germany
  2. Division of Basic Sciences, Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
  3. Institute for Cell Biology, University of Essen, Virchowstrasse 173, 45122 Essen, Germany
  4. Biological Instrumentation Programme, EMBL, Meyerhofstras zlige 1, 69117 Heidelberg, Germany

Correspondence to:

Martin Eilers, E-mail: Eilers@imt.uni-marburg.de

Received 7 April 2000; Accepted 8 September 2000; Revised 8 September 2000

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.

  • Keywords:

    • cell growth,
    • c-Myc,
    • cyclin E kinase,
    • E2F2,
    • p27