A model for a bistable biochemical trigger of mitosis

Bistable biochemical switching and the control of the events of the cell cycle*

“…Though the titration threshold is important in these examples, there are other biochemical mechanisms, without titratable inhibitors, for which the F and R curves may make the three intersections required for bistable switching, as already noted, and as shown elsewhere (Thron, 1996;1997a).…”

“…It has been proposed (Thron, 1994(Thron, , 1996, that the protein Suc1 acts as the inhibitor X in this model. Suc1 binds to Cdc2 and inhibits activation (Dunphy and Newport, 1989), and this mechanism could explain several of the puzzling e ects of Suc1 (Thron, 1994).…”

“…To analyse the mechanism we consider the case where the total of Cdc2 and Cdc2P is constant. Cdc2 is assumed to bind to the inhibitor X, but Cdc2P binding to X is assumed to be relatively much less strong (Thron, 1994(Thron, , 1996. Unbound Cdc2 e ectively (through activation of Cdc25) accelerates its own formation, i.e.…”

“…The model attributes it to the hypophosphorylated low-activity form of Cdc25 (Zheng and Ruderman, 1993;Thron, 1996).…”

“…Also, if curve F is not sigmoid, curvature in curve R may produce three intersections and bistability if R shows saturable (e.g. Michaelis-Menten) kinetics or if, as mentioned above, Wee1 activity decreases in M phase (Thron, 1996(Thron, , 1997a, Figure 4).…”