Cdk2-dependent phosphorylation of p27 facilitates its Myc-induced release from cyclin E/cdk2 complexes (original) (raw)

Oncogene volume 15, pages 2561–2576 (1997)Cite this article

Abstract

Activation of Myc triggers a rapid induction of cyclin E/cdk2 kinase activity and degradation of p27. Overt degradation of p27 is preceded by a specific dissociation of p27 from cyclin E/cdk2, but not from cyclin D/cdk4 complexes. We now show that cyclin E/cdk2 phosphorylates p27 at a carboxy-terminal threonine residue (T187) in vitro; mutation of this residue to valine stabilises cyclin E/cdk2 complexes. This reaction is not significantly inhibited by high concentrations of p27, suggesting that cdk2 bound to p27 is catalytically active. In vivo, p27 bound to cyclins E and A, but not to D-type cyclins is phosphorylated. Myc-induced release of p27 from cdk2 requires cdk2 kinase activity and is delayed in a T187V mutant of p27. After induction of Myc, p27 phosphorylated at threonine 187 transiently accumulates in a non cdk2 bound form. Our data suggest a mechanism in which p27 is released from cyclin E/cdk2 upon phosphorylation; in Myc-transformed cells, release is efficient as phosphorylated p27 is transiently bound in a non-cdk2 containing complex and subsequently degraded.

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Author notes

  1. Bettina Rudolph
    Present address: ICRF, P.O.Box 123, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK
  2. Philipp Steiner
    Present address: Whitehead Institute for Biomedical Research, 9 Cambridge Centre, Cambridge, 02142, MA, USA
  3. Martin Eilers
    Present address: Institute of Molecular Biology and Tumor Research (IMT),

Authors and Affiliations

  1. Zentrum für Molekulare Biologie Heidelberg (ZMBH), Im Neuenheimer Feld 282, Heidelberg, 69120, Germany
    Daniel Müller, Caroline Bouchard, Bettina Rudolph, Philipp Steiner & Martin Eilers
  2. Department of Neurobiology, University of Heidelberg, Im Neuenheimer Feld 364, Heidelberg, 69120, Germany
    Ingo Stuckmann & Wieland Huttner
  3. Biochemical Instrumentation Programme, EMBL, Meyerhofstr.1, Heidelberg, 69117, Germany
    Rainer Saffrich & Wilhelm Ansorge
  4. University of Marburg, Marburg, 35033, Germany
    Martin Eilers

Authors

  1. Daniel Müller
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  2. Caroline Bouchard
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  3. Bettina Rudolph
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  4. Philipp Steiner
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  5. Ingo Stuckmann
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  6. Rainer Saffrich
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  7. Wilhelm Ansorge
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  8. Wieland Huttner
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  9. Martin Eilers
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Müller, D., Bouchard, C., Rudolph, B. et al. Cdk2-dependent phosphorylation of p27 facilitates its Myc-induced release from cyclin E/cdk2 complexes.Oncogene 15, 2561–2576 (1997). https://doi.org/10.1038/sj.onc.1201440

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