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Short description

A Simple Mitotic Oscillator

Reference:Goldbeter A (1991)A minimal cascade model for the mitotic oscillator involving cyclin and cdc2 kinase, PNAS 88:9107-9111
Web Reference:http://www.pnas.org/cgi/content/abstract/88/20/9107

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Related Publication
  • A minimal cascade model for the mitotic oscillator involving cyclin and cdc2 kinase.
  • Goldbeter A
  • Proceedings of the National Academy of Sciences of the United States of America , 10/ 1991 , Volume 88 , pages: 9107-9111
  • Faculté des Sciences, Université Libre de Bruxelles, Belgium.
  • A minimal model for the mitotic oscillator is presented. The model, built on recent experimental advances, is based on the cascade of post-translational modification that modulates the activity of cdc2 kinase during the cell cycle. The model pertains to the situation encountered in early amphibian embryos, where the accumulation of cyclin suffices to trigger the onset of mitosis. In the first cycle of the bicyclic cascade model, cyclin promotes the activation of cdc2 kinase through reversible dephosphorylation, and in the second cycle, cdc2 kinase activates a cyclin protease by reversible phosphorylation. That cyclin activates cdc2 kinase while the kinase triggers the degradation of cyclin has suggested that oscillations may originate from such a negative feedback loop [Félix, M. A., Labbé, J. C., Dorée, M., Hunt, T. & Karsenti, E. (1990) Nature (London) 346, 379-382]. This conjecture is corroborated by the model, which indicates that sustained oscillations of the limit cycle type can arise in the cascade, provided that a threshold exists in the activation of cdc2 kinase by cyclin and in the activation of cyclin proteolysis by cdc2 kinase. The analysis shows how miototic oscillations may readily arise from time lags associated with these thresholds and from the delayed negative feedback provided by cdc2-induced cyclin degradation. A mechanism for the origin of the thresholds is proposed in terms of the phenomenon of zero-order ultrasensitivity previously described for biochemical systems regulated by covalent modification.
Contributors
Nicolas Le Novère

Metadata information

Curation status
Curated
  • Model originally submitted by : Nicolas Le Novère
  • Submitted: Sep 13, 2005 1:24:56 PM
  • Last Modified: May 16, 2013 3:38:01 PM
Revisions
  • Version: 2 public model Download this version
    • Submitted on: May 16, 2013 3:38:01 PM
    • Submitted by: Nicolas Le Novère
    • With comment: Current version of Goldbeter1991 - Min Mit Oscil
  • Version: 1 public model Download this version
    • Submitted on: Sep 13, 2005 1:24:56 PM
    • Submitted by: Nicolas Le Novère
    • With comment: Original import of Goldbeter1991_MinMitOscil
Curator's comment:
(added: 10 Aug 2009, 14:41:21, updated: 10 Aug 2009, 14:41:21)
Figure 3 of the reference publication is reproduced. The model was integrated and simulated using Copasi v4.5 (Build 20).