Abstract
A network of cyclin-dependent kinases (Cdks) based on intertwined negative and positive feedback loops regulates the mammalian cell cycle. We have recently proposed a skeleton model for this Cdk network, which incorporates Cdk regulation through phosphorylation-dephosphorylation and includes the positive feedback (PF) loops that underlie the dynamics of the G1/S and G2/M transitions of the cell cycle (Gérard et al., FEBS J., 279:3411–3431, 2012). We showed that the multiplicity of PF loops promotes the occurrence of bistability and increases the amplitude of oscillations in the various cyclin/Cdk complexes. Stochastic simulations further indicated that the presence of multiple PF loops enhances the robustness of Cdk oscillations with respect to molecular noise. Here we show that this skeleton model can produce complex modes of oscillatory behavior, which are due to the interaction between the multiple oscillatory circuits contained in the Cdk network driving the cell cycle.
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Acknowledgements
This work was supported by grant no. 3.4607.99 from the Fonds de la Recherche Scientifique Médicale (F.R.S.M., Belgium), the Belgian Federal Science Policy Office (IAP P6/25 “BioMaGNet”: “Bioinformatics and Modeling—From Genomes to Networks”), and the F.R.S.-FNRS (Belgium) in conjunction with the ErasysBio+ project C5Sys, “Circadian and Cell Cycle Clock Systems in Cancer”. C. Gérard currently holds a postdoctoral fellowship from the Foundation Philippe Wiener—Maurice Anspach in the Department of Biochemistry at the University of Oxford.
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Gérard, C., Goldbeter, A. (2013). Bistability and Oscillations in a Skeleton Model for the Cyclin/Cdk Network Driving the Mammalian Cell Cycle. In: Gilbert, T., Kirkilionis, M., Nicolis, G. (eds) Proceedings of the European Conference on Complex Systems 2012. Springer Proceedings in Complexity. Springer, Cham. https://doi.org/10.1007/978-3-319-00395-5_61
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DOI: https://doi.org/10.1007/978-3-319-00395-5_61
Publisher Name: Springer, Cham
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