CONTROL OF CELL-PROLIFERATION - TOWARDS N EW STRATEGIES SUGGESTED BY MODELING THE MITOTIC OSCILLATOR

The eukaryotic cell division cycle is governed by a biochemical oscill ator controlling the periodic onset of mitosis, This oscillator involv es a phosphorylation-dephosphorylation cascade that requires the synth esis of cyclin and results in the periodic activation of the cdc2 prot ein kinase, A minimal cascade model involving cyclin and cdc2 kinase a ccounts for the occurrence of sustained oscillations, The oscillations occur in a precise domain of parameter values I outside this domain, the cascade evolves towards a stable steady state corresponding to cel lular quiescence. The model suggests different ways to stop the mitoti c oscillator and, thereby, to control cell proliferation, Arrest of th e mitotic oscillator may occur upon inhibiting or activating the enzym es of the cascade beyond critical values that define the boundary betw een the absence or presence of sustained oscillations.