Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Biol Chem
2017 Jun 16;29224:10026-10034. doi: 10.1074/jbc.M117.778233.
Show Gene links
Show Anatomy links
Cell cycle-dependent regulation of Greatwall kinase by protein phosphatase 1 and regulatory subunit 3B.
Ren D
,
Fisher LA
,
Zhao J
,
Wang L
,
Williams BC
,
Goldberg ML
,
Peng A
.
???displayArticle.abstract??? Greatwall (Gwl) kinase plays an essential role in the regulation of mitotic entry and progression. Mitotic activation of Gwl requires both cyclin-dependent kinase 1 (CDK1)-dependent phosphorylation and its autophosphorylation at an evolutionarily conserved serine residue near the carboxyl terminus (Ser-883 in Xenopus). In this study we show that Gwl associates with protein phosphatase 1 (PP1), particularly PP1γ, which mediates the dephosphorylation of Gwl Ser-883. Consistent with the mitotic activation of Gwl, its association with PP1 is disrupted in mitotic cells and egg extracts. During mitotic exit, PP1-dependent dephosphorylation of Gwl Ser-883 occurs prior to dephosphorylation of other mitotic substrates; replacing endogenous Gwl with a phosphomimetic S883E mutant blocks mitotic exit. Moreover, we identified PP1 regulatory subunit 3B (PPP1R3B) as a targeting subunit that can direct PP1 activity toward Gwl. PPP1R3B bridges PP1 and Gwl association and promotes Gwl Ser-883 dephosphorylation. Consistent with the cell cycle-dependent association of Gwl and PP1, Gwl and PPP1R3B dissociate in M phase. Interestingly, up-regulation of PPP1R3B facilitates mitotic exit and blocks mitotic entry. Thus, our study suggests PPP1R3B as a new cell cycle regulator that functions by governing Gwl dephosphorylation.
,
,
Pubmed
,
,
Pubmed
,
Xenbase
,
,
Pubmed
,
Xenbase
Álvarez-Fernández,
Greatwall is essential to prevent mitotic collapse after nuclear envelope breakdown in mammals.
2013,
Pubmed
,
Xenbase
Anania,
Identification of thyroid tumor cell vulnerabilities through a siRNA-based functional screening.
2015,
Pubmed
Archambault,
Mutations in Drosophila Greatwall/Scant reveal its roles in mitosis and meiosis and interdependence with Polo kinase.
2007,
Pubmed
,
Xenbase
Blake-Hodek,
Determinants for activation of the atypical AGC kinase Greatwall during M phase entry.
2012,
Pubmed
,
Xenbase
Bollen,
Mitotic phosphatases: from entry guards to exit guides.
2009,
Pubmed
Burgess,
Loss of human Greatwall results in G2 arrest and multiple mitotic defects due to deregulation of the cyclin B-Cdc2/PP2A balance.
2010,
Pubmed
Castilho,
The M phase kinase Greatwall (Gwl) promotes inactivation of PP2A/B55delta, a phosphatase directed against CDK phosphosites.
2009,
Pubmed
,
Xenbase
da Cruz e Silva,
Differential expression of protein phosphatase 1 isoforms in mammalian brain.
1995,
Pubmed
Della Monica,
Fcp1 phosphatase controls Greatwall kinase to promote PP2A-B55 activation and mitotic progression.
2015,
Pubmed
Doherty,
Amino acid sequence and expression of the hepatic glycogen-binding (GL)-subunit of protein phosphatase-1.
1995,
Pubmed
Fisher,
Phosphatase 1 nuclear targeting subunit is an essential regulator of M-phase entry, maintenance, and exit.
2014,
Pubmed
,
Xenbase
Gharbi-Ayachi,
The substrate of Greatwall kinase, Arpp19, controls mitosis by inhibiting protein phosphatase 2A.
2010,
Pubmed
,
Xenbase
Glover,
The overlooked greatwall: a new perspective on mitotic control.
2012,
Pubmed
Goldberg,
Greatwall kinase protects mitotic phosphosites from barbarian phosphatases.
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
Hunt,
On the regulation of protein phosphatase 2A and its role in controlling entry into and exit from mitosis.
2013,
Pubmed
,
Xenbase
Kumagai,
Regulation of the cdc25 protein during the cell cycle in Xenopus extracts.
1992,
Pubmed
,
Xenbase
Lens,
Shared and separate functions of polo-like kinases and aurora kinases in cancer.
2010,
Pubmed
Lesage,
Interactor-mediated nuclear translocation and retention of protein phosphatase-1.
2004,
Pubmed
Li,
ASPP and iASPP: Implication in cancer development and progression.
2015,
Pubmed
Lorca,
The Greatwall kinase: a new pathway in the control of the cell cycle.
2013,
Pubmed
Ma,
Greatwall dephosphorylation and inactivation upon mitotic exit is triggered by PP1.
2016,
Pubmed
,
Xenbase
Ma,
How protein kinases co-ordinate mitosis in animal cells.
2011,
Pubmed
Manchado,
Targeting mitotic exit leads to tumor regression in vivo: Modulation by Cdk1, Mastl, and the PP2A/B55α,δ phosphatase.
2010,
Pubmed
Mochida,
Greatwall phosphorylates an inhibitor of protein phosphatase 2A that is essential for mitosis.
2010,
Pubmed
,
Xenbase
Mochida,
Two Bistable Switches Govern M Phase Entry.
2016,
Pubmed
Mochida,
Regulated activity of PP2A-B55 delta is crucial for controlling entry into and exit from mitosis in Xenopus egg extracts.
2009,
Pubmed
,
Xenbase
Moorhead,
Emerging roles of nuclear protein phosphatases.
2007,
Pubmed
Nagel,
Genome-wide siRNA Screen Identifies the Radiosensitizing Effect of Downregulation of MASTL and FOXM1 in NSCLC.
2015,
Pubmed
Nigg,
Mitotic kinases as regulators of cell division and its checkpoints.
2001,
Pubmed
Peng,
Serine/threonine phosphatases in the DNA damage response and cancer.
2010,
Pubmed
Peng,
Repo-man controls a protein phosphatase 1-dependent threshold for DNA damage checkpoint activation.
2010,
Pubmed
,
Xenbase
Peng,
Greatwall and Polo-like kinase 1 coordinate to promote checkpoint recovery.
2011,
Pubmed
,
Xenbase
Rebelo,
Protein phosphatase 1 is a key player in nuclear events.
2015,
Pubmed
Rogers,
PP1 initiates the dephosphorylation of MASTL, triggering mitotic exit and bistability in human cells.
2016,
Pubmed
Vera,
Greatwall promotes cell transformation by hyperactivating AKT in human malignancies.
2015,
Pubmed
Vigneron,
Greatwall maintains mitosis through regulation of PP2A.
2009,
Pubmed
,
Xenbase
Vigneron,
Characterization of the mechanisms controlling Greatwall activity.
2011,
Pubmed
,
Xenbase
Virshup,
From promiscuity to precision: protein phosphatases get a makeover.
2009,
Pubmed
Voets,
MASTL is the human orthologue of Greatwall kinase that facilitates mitotic entry, anaphase and cytokinesis.
2010,
Pubmed
,
Xenbase
Wang,
Mastl kinase, a promising therapeutic target, promotes cancer recurrence.
2014,
Pubmed
Wang,
Monoclonal antibodies against Xenopus greatwall kinase.
2011,
Pubmed
,
Xenbase
Wang,
Cell cycle regulation of Greatwall kinase nuclear localization facilitates mitotic progression.
2013,
Pubmed
Wang,
Spatial regulation of greatwall by Cdk1 and PP2A-Tws in the cell cycle.
2016,
Pubmed
Williams,
Greatwall-phosphorylated Endosulfine is both an inhibitor and a substrate of PP2A-B55 heterotrimers.
2014,
Pubmed
Wurzenberger,
Phosphatases: providing safe passage through mitotic exit.
2011,
Pubmed
Yanagida,
Protein phosphatases and cell division cycle control.
1992,
Pubmed
Yu,
Greatwall kinase participates in the Cdc2 autoregulatory loop in Xenopus egg extracts.
2006,
Pubmed
,
Xenbase
