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Proc Natl Acad Sci U S A
2013 Oct 22;11043:17374-9. doi: 10.1073/pnas.1310745110.
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Greatwall is essential to prevent mitotic collapse after nuclear envelope breakdown in mammals.
Álvarez-Fernández M
,
Sánchez-Martínez R
,
Sanz-Castillo B
,
Gan PP
,
Sanz-Flores M
,
Trakala M
,
Ruiz-Torres M
,
Lorca T
,
Castro A
,
Malumbres M
.
???displayArticle.abstract??? Greatwall is a protein kinase involved in the inhibition of protein phosphatase 2 (PP2A)-B55 complexes to maintain the mitotic state. Although its biochemical activity has been deeply characterized in Xenopus, its specific relevance during the progression of mitosis is not fully understood. By using a conditional knockout of the mouse ortholog, Mastl, we show here that mammalian Greatwall is essential for mouse embryonic development and cell cycle progression. Yet, Greatwall-null cells enter into mitosis with normal kinetics. However, these cells display mitotic collapse after nuclear envelope breakdown (NEB) characterized by defective chromosome condensation and prometaphase arrest. Intriguingly, Greatwall is exported from the nucleus to the cytoplasm in a CRM1-dependent manner before NEB. This export occurs after the nuclear import of cyclin B-Cdk1 complexes, requires the kinase activity of Greatwall, and is mediated by Cdk-, but not Polo-like kinase 1-dependent phosphorylation. The mitotic collapse observed in Greatwall-deficient cells is partially rescued after concomitant depletion of B55 regulatory subunits, which are mostly cytoplasmic before NEB. These data suggest that Greatwall is an essential protein in mammals required to prevent mitotic collapse after NEB.
Archambault,
Mutations in Drosophila Greatwall/Scant reveal its roles in mitosis and meiosis and interdependence with Polo kinase.
2007, Pubmed,
Xenbase
Archambault,
Mutations in Drosophila Greatwall/Scant reveal its roles in mitosis and meiosis and interdependence with Polo kinase.
2007,
Pubmed
,
Xenbase
Bettencourt-Dias,
Genome-wide survey of protein kinases required for cell cycle progression.
2004,
Pubmed
Blake-Hodek,
Determinants for activation of the atypical AGC kinase Greatwall during M phase entry.
2012,
Pubmed
,
Xenbase
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
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
Hagting,
Translocation of cyclin B1 to the nucleus at prophase requires a phosphorylation-dependent nuclear import signal.
1999,
Pubmed
Hagting,
MPF localization is controlled by nuclear export.
1998,
Pubmed
Hara,
Greatwall kinase and cyclin B-Cdk1 are both critical constituents of M-phase-promoting factor.
2012,
Pubmed
,
Xenbase
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
Peng,
A novel role for greatwall kinase in recovery from DNA damage.
2010,
Pubmed
,
Xenbase
Potapova,
Mitotic progression becomes irreversible in prometaphase and collapses when Wee1 and Cdc25 are inhibited.
2011,
Pubmed
,
Xenbase
Rangone,
Suppression of scant identifies Endos as a substrate of greatwall kinase and a negative regulator of protein phosphatase 2A in mitosis.
2011,
Pubmed
Santos,
Spatial positive feedback at the onset of mitosis.
2012,
Pubmed
Tuck,
Robust mitotic entry is ensured by a latching switch.
2013,
Pubmed
Vigneron,
Greatwall maintains mitosis through regulation of PP2A.
2009,
Pubmed
,
Xenbase
Vigneron,
Characterization of the mechanisms controlling Greatwall activity.
2011,
Pubmed
,
Xenbase
Voets,
MASTL is the human orthologue of Greatwall kinase that facilitates mitotic entry, anaphase and cytokinesis.
2010,
Pubmed
,
Xenbase
Wang,
PP2A-twins is antagonized by greatwall and collaborates with polo for cell cycle progression and centrosome attachment to nuclei in drosophila embryos.
2011,
Pubmed
Wang,
Cell cycle regulation of Greatwall kinase nuclear localization facilitates mitotic progression.
2013,
Pubmed
White-Cooper,
Mutations in new cell cycle genes that fail to complement a multiply mutant third chromosome of Drosophila.
1996,
Pubmed
Yu,
Greatwall kinase participates in the Cdc2 autoregulatory loop in Xenopus egg extracts.
2006,
Pubmed
,
Xenbase
Yu,
Greatwall kinase: a nuclear protein required for proper chromosome condensation and mitotic progression in Drosophila.
2004,
Pubmed
