Towards a blueprint of the cell cycle

Oncogene
L AlberghinaL Cazzador

Abstract

The understanding of the organisation of cell cycle events is of utmost importance to devise effective therapeutic strategies for cancer. In this article we gather evidences from the literature in support of a system model of the cell cycle, in which a growth-sensitive threshold controls entry into S phase and the sequential activation of cyclin-dependent kinases. The cycle is terminated by an End function, that comprises events from the onset of mitosis to cell division and that may also be modulated by the increase of cell size. This blueprint allows quantitative predictions by computer simulations of steady and transitory states. In fact, we show that the proposed control system applies to budding yeast populations during nutritional shift-up and following hyperactivation of the cAMP signalling pathway. Besides the growth-sensitive control system it is shown to apply to mammalian cells both in the exit from quiescence and in active proliferation. The putative molecular determinants that set the threshold controlling S phase entry are consistently altered in cancer cells. Finally, we discuss an input/output analysis based on the simulated behaviour derived from the blueprint as a new tool to investigate the road to cancer.

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Citations

Dec 19, 2003·FEMS Microbiology Letters·Danilo PorroLilia Alberghina
Apr 17, 2007·PLoS Computational Biology·Matteo BarberisLilia Alberghina
Oct 1, 2004·Chembiochem : a European Journal of Chemical Biology·Lilia AlberghinaMarco Vanoni
Dec 17, 2008·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Danilo PorroChristos Hatzis
Oct 10, 2002·American Journal of Physiology. Cell Physiology·Sybille RexNawfal W Istfan
Jan 26, 2005·Biochemical Society Transactions·M VanoniL Alberghina

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