PP2A/B55 and Fcp1 regulate Greatwall and Ensa desphorylation during mitotic exit

Hegarat, Nadia, Vesely, Clare, Peter, Nisha, Oliver, Antony and Hochegger, Helfrid (2014) PP2A/B55 and Fcp1 regulate Greatwall and Ensa desphorylation during mitotic exit. PLoS Genetics, 10 (2). e1004259 1-12. ISSN 1553-7390

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Abstract

Entry into mitosis is triggered by activation of Cdk1 and inactivation of its counteracting phosphatase PP2A/B55. Greatwall kinase inactivates PP2A/B55 via its substrates Ensa and ARPP19. Both Greatwall and Ensa/ARPP19 are regulated by phosphorylation, but the dynamic regulation of Greatwall activity and the phosphatases that control Greatwall kinase and its substrates are poorly understood. To address these questions we applied a combination of mathematical modelling and experiments using phospho-specific antibodies to monitor Greatwall, Ensa/ARPP19 and Cdk substrate phosphorylation during mitotic entry and exit. We demonstrate that PP2A/B55 is required for Gwl dephosphorylation at the essential Cdk site Thr194. Ensa/ARPP19 dephosphorylation is mediated by the RNA Polymerase II carboxy terminal domain phosphatase Fcp1. Surprisingly, neither Fcp1 nor PP2A appear to essential to dephosphorylate the bulk of mitotic Cdk1 substrates following Cdk1 inhibition. Taken together our results suggest a hierarchy of phosphatases coordinating Greatwall, Ensa/ARPP19 and Cdk substrate dephosphorylation during mitotic exit.

Item Type: Article
Schools and Departments: School of Life Sciences > Biochemistry
School of Life Sciences > Sussex Centre for Genome Damage and Stability
Research Centres and Groups: Genome Damage and Stability Centre
Subjects: Q Science > Q Science (General)
Depositing User: Sarah Frances
Date Deposited: 13 Dec 2018 12:39
Last Modified: 13 Dec 2018 12:41
URI: http://sro.sussex.ac.uk/id/eprint/80759

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Project NameSussex Project NumberFunderFunder Ref
Exploiting chemical genetics to investigate the control of microtubule dynamics by mitotic kinasesG0900CANCER RESEARCH UKC28206/A14499