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Senimar : de Claude Gérard

par Webmestre - publié le , mis à jour le

"Dynamics of the cyclin-dependent kinase network driving the cell cycle"

Jeudi 17 octobre à 11 heures, en salle de conférences du CERLA

Claude Gérard, Post-doctoral research associate, de Duve Institute, Université Catholique de Louvain.

The cell division process plays an important role for unicellular and pluricellular organisms. In the latter, it drives the development from fertilised eggs into mature organisms. Failure to control the p ! recise temporal order of the cell cycle can result in tumour proliferation and cancer development. We proposed an integrated computational model for the network of cyclin-dependent kinases (Cdks) that controls the dynamics of the mammalian cell cycle. The model contains four Cdk modules regulated by intertwined positive and negative feedback loops. We will show that the model accounts for many properties of the mammalian cell cycle. Moreover, we determined the effect of positive feedback (PF) loops in phosphorylation/dephosphorylation cycles on the dynamics of the Cdk network. Using stochastic simulations, we further show that the presence of PF loops in the cell cycle markedly enhances its robustness with respect to molecular noise. Finally, using simple computational models, we showed that the ordered phosphorylation of cellular proteins allowing a correct progression in the cell cycle could be explained solely by mult ! i-site phosphorylation/dephosphorylation and competition of substrates ! for interconverting kinase (Cdk) and phosphatase. Since these latter models lack the elaborate control systems characteristic of modern eukaryotes, they could represent the cell cycle control mechanism of primitive cells before the current cell cycle control network evolved in all its complexity.