Modeling the Cell Division Cycle: M-phase Trigger, Oscillations, and Size Control

Abstract The proteins Cdc2 and cyclin form a heterodimer, called M-phase promoting factor (MPF), that controls the transition from interphase to mitosis of the cell cycle. The Cdc2-cyclin regulatory system can operate either as a spontaneous oscillator in early embryos, or as an excitable switch in growth-controlled cell division. We develop a mathematical model of the interactions among the subunits of MPF (Cdc2 and cyclin) and the enzymes (Wee1, Cdc25, CAK and INH) which together control the phosphorylation state of Cdc2. The model explains how, in the switch mode, the Wee1/Cdc25 ratio can serve as a proxy for the cell's nucleocytoplasmic ratio: triggering mitosis and cell division each time the mass of a growing cell doubles, in order to maintain a state of balanced growth and division.