title: Dynamics of the mammalian cell cycle in physiological and pathological conditions.
abstract: A network of cyclin-dependent kinases (Cdks) controls progression along the successive phases G1, S, G2, and M of the mammalian cell cycle. Deregulations in the expression of molecular components in this network often lead to abusive cell proliferation and cancer. Given the complex nature of the Cdk network, it is fruitful to resort to computational models to grasp its dynamical properties. Investigated by means of bifurcation diagrams, a detailed computational model for the Cdk network shows how the balance between quiescence and proliferation is affected by activators (oncogenes) and inhibitors (tumor suppressors) of cell cycle progression, as well as by growth factors and other external factors such as the extracellular matrix (ECM) and cell contact inhibition. Suprathreshold changes in all these factors can trigger a switch in the dynamical behavior of the network corresponding to a bifurcation between a stable steady state, associated with cell cycle arrest, and sustained oscillations of the various cyclin/Cdk complexes, corresponding to cell proliferation. The model for the Cdk network accounts for the dependence or independence of cell proliferation on serum and/or cell anchorage to the ECM. Such computational approach provides an integrated view of the control of cell proliferation in physiological or pathological conditions. Whether the balance is tilted toward cell cycle arrest or cell proliferation depends on the direction in which the threshold associated with the bifurcation is passed once the cell integrates the multiple signals, internal or external to the Cdk network, that promote or impede progression in the cell cycle.
authors.affiliation: Unité de Chronobiologie théorique, Faculté des Sciences, Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors.forename: Claude
authors.initials: C
authors.lastname: Gérard
authors.affiliation: Unité de Chronobiologie théorique, Faculté des Sciences, Université Libre de Bruxelles (ULB), Brussels, Belgium.|Stellenbosch Institute for Advanced Study (STIAS), Wallenberg Research Centre at Stellenbosch University, Marais Street, Stellenbosch, South Africa.
authors.forename: Albert
authors.initials: A
authors.lastname: Goldbeter
mesh_terms: D000818:Animals; D002453:Cell Cycle; D003198:Computer Simulation; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological
chemical_list: D018844:Cyclin-Dependent Kinases