Myc activation of cyclin E/Cdk2 kinase involves induction of cyclin E gene transcription and inhibition of p27Kip1 binding to newly formed complexes (original) (raw)

Oncogene volume 14, pages 2373–2381 (1997)Cite this article

Abstract

Induction of the Myc-oestrogen receptor fusion protein (MycER) by 4-OH-tamoxifen (OHT) leads to the activation of Cyclin E/Cyclin-dependent kinase 2 (CycE/Cdk2) complexes followed by the induction of DNA synthesis. As CycE/Cdk2 activity is essential for G1/S transition, we have investigated the mechanism by which Myc can activiate CycE/Cdk2. Our results suggest that this activation may involve at least two Myc-dependent steps: the induction of cyclin E gene transcription followed by accumulation of cyclin E mRNA in a protein synthesis-independent manner and the inhibition of p27Kip1 association with CycE/Cdk2 complexes containing newly synthesised CycE. As a consequence phosphorylation of CycE-bound Cdk2 by cyclin activating kinase (CAK) is accelerated. We propose a model in which the active newly synthesised CycE/Cdk2 complexes trigger a positive feed-back mechanism to activate preexisting complexes through phosphorylation-dependent p27Kip1 release.

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Authors and Affiliations

  1. Imperial Cancer Research Fund, Lincoln's Inn Fields, London, WC2A 3PX, UK
    Ignacio Pérez-Roger, David LC Solomon, Andreas Sewing & Hartmut Land

Authors

  1. Ignacio Pérez-Roger
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  2. David LC Solomon
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  3. Andreas Sewing
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  4. Hartmut Land
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Pérez-Roger, I., Solomon, D., Sewing, A. et al. Myc activation of cyclin E/Cdk2 kinase involves induction of cyclin E gene transcription and inhibition of p27Kip1 binding to newly formed complexes.Oncogene 14, 2373–2381 (1997). https://doi.org/10.1038/sj.onc.1201197

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