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.

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 50 print issues and online access

$259.00 per year

only $5.18 per issue

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

Similar content being viewed by others

Author information

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
    You can also search for this author inPubMed Google Scholar
  2. David LC Solomon
    You can also search for this author inPubMed Google Scholar
  3. Andreas Sewing
    You can also search for this author inPubMed Google Scholar
  4. Hartmut Land
    You can also search for this author inPubMed Google Scholar

Rights and permissions

About this article

Cite this article

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

Download citation

Keywords

This article is cited by