Bistable biochemical switching and the control of the events of the cell cycle.
Some of the events of the cell cycle appear to be triggered by a bistable mechanism. A bistable biochemical system can respond to a small, slow signal and is carried by positive feedback from one stable steady state directly to another, in an all-or-none manner. Slow or subthreshold stimuli do not cause accommodation or loss of excitability. Switching is not readily reversible by removing the stimulus, i.e. there is hysteresis: reversal generally requires a stronger, opposite stimulus. Biochemically, bistable biochemical switching requires positive feedback, and mechanisms for stabilizing the system against premature activation and for destabilization in response to a biological signal. Three bistable biochemical models, all suggested by reported experimental observations, are described and analysed. These models suggest that a titratable inhibitor may play an important part in bistable switching, because the end-point of titration can form a natural threshold for enhancement of positive feedback.
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Department of Pharmacology and Toxicology, Darmouth Medical School, Hanover, NH 03755, USA.
D002352:Carrier Proteins; D002384:Catalysis; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D016213:Cyclins / Q000502:physiology; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D004789:Enzyme Activation; D005246:Feedback; D016161:Genes, Retinoblastoma; D016259:Genes, myc; D007700:Kinetics; D008954:Models, Biological; D011401:Promoter Regions, Genetic; D056465:Retinoblastoma-Binding Protein 1; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D016213:Cyclins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D056465:Retinoblastoma-Binding Protein 1; D014157:Transcription Factors; D018844:Cyclin-Dependent Kinases