title: Model scenarios for switch-like mitotic transitions.
abstract: To facilitate rapid accumulation of Cdk1-phosphorylated substrate proteins, the Cdk1 counter-acting phosphatase, PP2A-B55 is inhibited during M phase by stoichiometric inhibitors (ENSA and Arpp19). These inhibitors are activated when phosphorylated by Cdk1-activated Greatwall-kinase. Recent experiments show that ENSA is dephosphorylated and inactivated by the PP2A-B55 itself, and acts as an unfair substrate inhibiting PP2A-B55 activity towards other Cdk1 substrates. Mathematical modelling shows that this mutual antagonism between the phosphatase and its inhibitor is insufficient to explain the switch-like characteristics of mitotic entry and exit. We show that the feedback regulation of Greatwall activating kinase and/or inactivating phosphatase can explain the abruptness of these cell cycle transitions.
authors: OCISB, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors: P K
authors: PK
authors: Vinod
authors: OCISB, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK. Electronic address: bela.novak@bioch.ox.ac.uk.
authors: Bela
authors: B
authors: Novak
mesh_terms: D000465:Algorithms; D016203:CDC2 Protein Kinase; D018844:Cyclin-Dependent Kinases / Q000502:physiology; D025461:Feedback, Physiological; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008938:Mitosis; D008954:Models, Biological; D010455:Peptides / Q000502:physiology; D010750:Phosphoproteins / Q000502:physiology; D054648:Protein Phosphatase 2 / Q000502:physiology; D015398:Signal Transduction
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D010750:Phosphoproteins; C064321:cyclic AMP-regulated phosphoprotein 19; C075663:endosulfine; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases; D054648:Protein Phosphatase 2
keywords: Biochemical kinetics; Bistability; Greatwall-kinase; Mitotic control; Phosphatase