journal.pgen.1004004.PDF (7.87 MB)
PP2A/B55 and Fcp1 regulate Greatwall and Ensa desphorylation during mitotic exit
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 HocheggerEntry 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 GeneticsISSN
1553-7390Publisher
Public Library of ScienceExternal DOI
Issue
2Volume
10Page range
1Article number
e1004259Department affiliated with
- Biochemistry Publications
Research groups affiliated with
- Genome Damage and Stability Centre Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2018-12-13First Open Access (FOA) Date
2018-12-13First Compliant Deposit (FCD) Date
2018-12-13Usage metrics
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