Exit from mitosis induced by a calcium transient: the relation to the MPF and InsP3 dynamics.

Cells divide only after passing through a control point in late G1. This passage is followed by the accumulation of the mitotic cyclin which binds to p34cdc2, allowing for the subsequent phosphorylation and dephosphorylation of the latter protein. It is the active MPF, i.e. the phosphorylated mitotic cyclin-p34cdc2 kinase complex that triggers entry into mitosis. MPF becomes increasingly active as the cell forwards to anaphase, when a sudden increase in InsP3 takes place. This in turn induces a large Ca2+ release in cytosol from internal calcium stores and a calcium-dependent positive feedback control on InsP3-induced calcium release enhances the effect on InsP3-mediated Ca2+ transient. Meanwhile, empty calcium stores signal to plasma membrane for a constant calcium influx at high InsP3 levels. The cytosolic calcium excess is assumed to activate the CaMKll holloenzyme which involves the production of the ubiquitination complex necessary for cyclin degradation and MPF inactivation. Accordingly, a mathematical model was proposed by means of an eight-dimensional dynamical system that yields the time dependence of the main cellular quantities in a picture of the mitosis specific events.