A model for a bistable biochemical trigger of mitosis.
The activation of maturation promoting factor (MPF, cyclin B/Cdc2), which starts mitosis, is modeled as a bistable biochemical switch or trigger. A small, slow parameter change can cause an abrupt transition by a saddle-node bifurcation from a stable steady state of low activity to one of high activity. The switch is not reversed if the parameter change is reversed (hysteresis). The dynamical features necessary for this triggering action are the presence of two stable steady states (low-activity and high-activity), and one unstable steady state. The key biochemical kinetic features of the model are (1) mutual activation by MPF and Cdc25, which makes the activation of MPF effectively autocatalytic, and (2) binding of MPF by Suc1, which inhibits MPF autocatalysis and stabilizes the low-activity steady state until the amount of MPF begins to approach or exceed stoichiometrically the amount of Suc1, then allows strong autocatalysis and full activation. The special virtues of bistable triggering, and the general types of biochemical mechanism which can produce it, are discussed.
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Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, NH 03755-3835, USA.
D016203:CDC2 Protein Kinase / Q000502:physiology; D018797:Cell Cycle Proteins; D016213:Cyclins / Q000502:physiology; D005656:Fungal Proteins / Q000502:physiology; D008432:Mathematical Computing; D016200:Maturation-Promoting Factor / Q000502:physiology*; D008938:Mitosis / Q000502:physiology*; D008954:Models, Biological; D029702:Schizosaccharomyces pombe Proteins
D018797:Cell Cycle Proteins; D016213:Cyclins; D005656:Fungal Proteins; D029702:Schizosaccharomyces pombe Proteins; C051655:Suc1 protein, S pombe; D016203:CDC2 Protein Kinase; D016200:Maturation-Promoting Factor