Title |
A PP1–PP2A phosphatase relay controls mitotic progression
|
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Published in |
Nature, December 2014
|
DOI | 10.1038/nature14019 |
Pubmed ID | |
Authors |
Agnes Grallert, Elvan Boke, Anja Hagting, Ben Hodgson, Yvonne Connolly, John R. Griffiths, Duncan L. Smith, Jonathon Pines, Iain M. Hagan |
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. |
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Mendeley readers
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Unknown | 290 | 96% |
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Researcher | 70 | 23% |
Student > Master | 39 | 13% |
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Student > Doctoral Student | 15 | 5% |
Other | 40 | 13% |
Unknown | 31 | 10% |
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Biochemistry, Genetics and Molecular Biology | 109 | 36% |
Chemistry | 12 | 4% |
Medicine and Dentistry | 11 | 4% |
Computer Science | 4 | 1% |
Other | 13 | 4% |
Unknown | 31 | 10% |