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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.

Original publication

DOI

10.1016/j.febslet.2015.02.007

Type

Journal article

Journal

FEBS Lett

Publication Date

12/03/2015

Volume

589

Pages

667 - 671

Keywords

Biochemical kinetics, Bistability, Greatwall-kinase, Mitotic control, Phosphatase, Algorithms, Cyclin-Dependent Kinases, Feedback, Physiological, Humans, Mitosis, Models, Biological, Peptides, Phosphoproteins, Protein Phosphatase 2, Signal Transduction