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

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Version 2 2023-06-12, 08:55
Version 1 2023-06-09, 16:13
journal contribution
posted on 2023-06-12, 08:55 authored by Nadia Hegarat, Clare NeilClare Neil, Nisha Peter, Antony OliverAntony Oliver, Helfrid HocheggerHelfrid Hochegger
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.

Funding

Exploiting chemical genetics to investigate the control of microtubule dynamics by mitotic kinases; G0900; CANCER RESEARCH UK; C28206/A14499

History

Publication status

  • Published

File Version

  • Published version

Journal

PLoS Genetics

ISSN

1553-7390

Publisher

Public Library of Science

Issue

2

Volume

10

Page range

1

Article number

e1004259

Department affiliated with

  • Biochemistry Publications

Research groups affiliated with

  • Genome Damage and Stability Centre Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2018-12-13

First Open Access (FOA) Date

2018-12-13

First Compliant Deposit (FCD) Date

2018-12-13

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