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FEBS Lett. 2015 Mar 12;589(6):667-71. doi: 10.1016/j.febslet.2015.02.007. Epub 2015 Feb 12.

Model scenarios for switch-like mitotic transitions.

Author information

1
OCISB, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
2
OCISB, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK. Electronic address: bela.novak@bioch.ox.ac.uk.

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.

KEYWORDS:

Biochemical kinetics; Bistability; Greatwall-kinase; Mitotic control; Phosphatase

PMID:
25683003
DOI:
10.1016/j.febslet.2015.02.007
[Indexed for MEDLINE]
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