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Molecular Systems Biology of Sic1 in Yeast Cell Cycle Regulation Through Multiscale Modeling

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Advances in Systems Biology

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 736))

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Abstract

Cell cycle control is highly regulated to guarantee the precise timing of events essential for cell growth, i.e., DNA replication onset and cell division. Failure of this control plays a role in cancer and molecules called cyclin-dependent kinase (Cdk) inhibitors (Ckis) exploit a critical function in cell cycle timing. Here we present a multiscale modeling where experimental and computational studies have been employed to investigate structure, function and temporal dynamics of the Cki Sic1 that regulates cell cycle progression in Saccharomyces cerevisiae. Structural analyses reveal molecular details of the interaction between Sic1 and Cdk/cyclin complexes, and biochemical investigation reveals Sic1 function in analogy to its human counterpart p27Kip1, whose deregulation leads to failure in timing of kinase activation and, therefore, to cancer. Following these findings, a bottom-up systems biology approach has been developed to characterize modular networks addressing Sic1 regulatory function. Through complementary experimentation and modeling, we suggest a mechanism that underlies Sic1 function in controlling temporal waves of cyclins to ensure correct timing of the phase-specific Cdk activities.

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Acknowledgements

MB is supported by grants from the European Commission ENFIN (contract number LSHGCT-2005–518254) and UNICELLSYS (contract number HEALTH-2007–201142) to EK. I would like to thank Edda Klipp and Lilia Alberghina for their constant scientific support in the course of my research, and Marco Vanoni, Luca De Gioia, and Francesc Posas for stimulating discussions.

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  1. Institute for Biology, Humboldt University Berlin, Invalidenstr. 42, 10115, Berlin, Germany

    Matteo Barberis

  2. Max Planck Institute for Molecular Genetics, Ihnestr. 73, 14195, Berlin, Germany

    Matteo Barberis

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  1. School of Informatics, University of Edinburgh, Crichton Street 10, Edinburgh, EH89AB, UK

    Igor I. Goryanin

  2. School of Biological Sciences, University of Edinburgh, Mayfield Road, Edinburgh, EH93JR, UK

    Andrew B. Goryachev

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Barberis, M. (2012). Molecular Systems Biology of Sic1 in Yeast Cell Cycle Regulation Through Multiscale Modeling. In: Goryanin, I.I., Goryachev, A.B. (eds) Advances in Systems Biology. Advances in Experimental Medicine and Biology, vol 736. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7210-1_7

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