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Nature. 2015 Jan 1;517(7532):94-98. doi: 10.1038/nature14019. Epub 2014 Dec 10.

A PP1-PP2A phosphatase relay controls mitotic progression.

Author information

1
Cell Division Group, CRUK Manchester Institute, University of Manchester, Wilmslow Road, Manchester, M20 4BX, UK.
2
The Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK.
3
Biological Mass Spectrometry, CRUK Manchester Institute, University of Manchester, Wilmslow Road, Manchester, M20 4BX, UK.
#
Contributed equally

Abstract

The widespread reorganization of cellular architecture in mitosis is achieved through extensive protein phosphorylation, driven by the coordinated activation of a mitotic kinase network and repression of counteracting phosphatases. Phosphatase activity must subsequently be restored to promote mitotic exit. Although Cdc14 phosphatase drives this reversal in budding yeast, protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) activities have each been independently linked to mitotic exit control in other eukaryotes. Here we describe a mitotic phosphatase relay in which PP1 reactivation is required for the reactivation of both PP2A-B55 and PP2A-B56 to coordinate mitotic progression and exit in fission yeast. The staged recruitment of PP1 (the Dis2 isoform) to the regulatory subunits of the PP2A-B55 and PP2A-B56 (B55 also known as Pab1; B56 also known as Par1) holoenzymes sequentially activates each phosphatase. The pathway is blocked in early mitosis because the Cdk1-cyclin B kinase (Cdk1 also known as Cdc2) inhibits PP1 activity, but declining cyclin B levels later in mitosis permit PP1 to auto-reactivate. PP1 first reactivates PP2A-B55; this enables PP2A-B55 in turn to promote the reactivation of PP2A-B56 by dephosphorylating a PP1-docking site in PP2A-B56, thereby promoting the recruitment of PP1. PP1 recruitment to human, mitotic PP2A-B56 holoenzymes and the sequences of these conserved PP1-docking motifs suggest that PP1 regulates PP2A-B55 and PP2A-B56 activities in a variety of signalling contexts throughout eukaryotes.

PMID:
25487150
PMCID:
PMC4338534
DOI:
10.1038/nature14019
[Indexed for MEDLINE]
Free PMC Article

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