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Entry into mitosis is mediated by the phosphorylation of key cell cycle regulators by cyclin-dependent kinase 1 (Cdk1). In Xenopus embryos, the M-phase-promoting activity of Cdk1 is antagonized by protein phosphatase PP2A-B55. Hence, to ensure robust cell cycle transitions, Cdk1 and PP2A-B55 must be regulated so that their activities are mutually exclusive. The mechanism underlying PP2A-B55 inactivation at mitotic entry is well understood: Cdk1-activated Greatwall (Gwl) kinase phosphorylates Ensa/Arpp19, thereby enabling them to bind to and inhibit PP2A-B55. However, the re-activation of PP2A-B55 during mitotic exit, which is essential for cell cycle progression, is less well understood. Here, we identify protein phosphatase PP1 as an essential component of the PP2A-B55 re-activation pathway in Xenopus embryo extracts. PP1 initiates the re-activation of PP2A-B55 by dephosphorylating Gwl. We provide evidence that PP1 targets the auto-phosphorylation site of Gwl, resulting in efficient Gwl inactivation. This step is necessary to facilitate subsequent complete dephosphorylation of Gwl by PP2A-B55. Thus, by identifying PP1 as the phosphatase initiating Gwl inactivation, our study provides the molecular explanation for how Cdk1 inactivation is coupled to PP2A-B55 re-activation at mitotic exit.
Beullens,
The C-terminus of NIPP1 (nuclear inhibitor of protein phosphatase-1) contains a novel binding site for protein phosphatase-1 that is controlled by tyrosine phosphorylation and RNA binding.
2000, Pubmed
Beullens,
The C-terminus of NIPP1 (nuclear inhibitor of protein phosphatase-1) contains a novel binding site for protein phosphatase-1 that is controlled by tyrosine phosphorylation and RNA binding.
2000,
Pubmed
Blake-Hodek,
Determinants for activation of the atypical AGC kinase Greatwall during M phase entry.
2012,
Pubmed
,
Xenbase
Bollen,
The structure, role, and regulation of type 1 protein phosphatases.
1992,
Pubmed
Castilho,
The M phase kinase Greatwall (Gwl) promotes inactivation of PP2A/B55delta, a phosphatase directed against CDK phosphosites.
2009,
Pubmed
,
Xenbase
Clarke,
Dephosphorylation of cdc25-C by a type-2A protein phosphatase: specific regulation during the cell cycle in Xenopus egg extracts.
1993,
Pubmed
,
Xenbase
Cundell,
The BEG (PP2A-B55/ENSA/Greatwall) pathway ensures cytokinesis follows chromosome separation.
2013,
Pubmed
Dohadwala,
Phosphorylation and inactivation of protein phosphatase 1 by cyclin-dependent kinases.
1994,
Pubmed
Ferrigno,
Protein phosphatase 2A1 is the major enzyme in vertebrate cell extracts that dephosphorylates several physiological substrates for cyclin-dependent protein kinases.
1993,
Pubmed
,
Xenbase
Gharbi-Ayachi,
The substrate of Greatwall kinase, Arpp19, controls mitosis by inhibiting protein phosphatase 2A.
2010,
Pubmed
,
Xenbase
Grallert,
A PP1-PP2A phosphatase relay controls mitotic progression.
2015,
Pubmed
Hégarat,
PP2A/B55 and Fcp1 regulate Greatwall and Ensa dephosphorylation during mitotic exit.
2014,
Pubmed
Hershko,
Mechanisms and regulation of the degradation of cyclin B.
1999,
Pubmed
,
Xenbase
King,
A 20S complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B.
1995,
Pubmed
,
Xenbase
Kwon,
Cell cycle-dependent phosphorylation of mammalian protein phosphatase 1 by cdc2 kinase.
1997,
Pubmed
Manchado,
Targeting mitotic exit leads to tumor regression in vivo: Modulation by Cdk1, Mastl, and the PP2A/B55α,δ phosphatase.
2010,
Pubmed
Mayer-Jaekel,
Drosophila mutants in the 55 kDa regulatory subunit of protein phosphatase 2A show strongly reduced ability to dephosphorylate substrates of p34cdc2.
1994,
Pubmed
Mochida,
Greatwall phosphorylates an inhibitor of protein phosphatase 2A that is essential for mitosis.
2010,
Pubmed
,
Xenbase
Mochida,
PP1 inactivates Greatwall to release PP2A-B55 from mitotic confinement.
2015,
Pubmed
,
Xenbase
Mochida,
Regulated activity of PP2A-B55 delta is crucial for controlling entry into and exit from mitosis in Xenopus egg extracts.
2009,
Pubmed
,
Xenbase
Schmitz,
Live-cell imaging RNAi screen identifies PP2A-B55alpha and importin-beta1 as key mitotic exit regulators in human cells.
2010,
Pubmed
Tischer,
The APC/C inhibitor XErp1/Emi2 is essential for Xenopus early embryonic divisions.
2012,
Pubmed
,
Xenbase
Vigneron,
Greatwall maintains mitosis through regulation of PP2A.
2009,
Pubmed
,
Xenbase
Vigneron,
Characterization of the mechanisms controlling Greatwall activity.
2011,
Pubmed
,
Xenbase
Vinod,
Model scenarios for switch-like mitotic transitions.
2015,
Pubmed
Williams,
Greatwall-phosphorylated Endosulfine is both an inhibitor and a substrate of PP2A-B55 heterotrimers.
2014,
Pubmed
Wu,
PP1-mediated dephosphorylation of phosphoproteins at mitotic exit is controlled by inhibitor-1 and PP1 phosphorylation.
2009,
Pubmed
,
Xenbase
