[Control of cell proliferation: towards new strategies suggested by modelling the mitotic oscillator]

The eukaryotic cell division cycle is governed by a biochemical oscillator controlling the periodic onset of mitosis. This oscillator involves a phosphorylation-dephosphorylation cascade that requires the synthesis of cyclin and results in the periodic activation of the cdc2 protein kinase. A minimal cascade model involving cyclin and cdc2 kinase accounts for the occurrence of sustained oscillations. The oscillations occur in a precise domain of parameter values; outside this domain, the cascade evolves towards a stable steady state corresponding to cellular quiescence. The model suggests different ways to stop the mitotic oscillator and, thereby, to control cell proliferation. Arrest of the mitotic oscillator may occur upon inhibiting or activating the enzymes of the cascade beyond critical values that define the boundary between the absence or presence of sustained oscillations.