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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.
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,
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,
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,
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,
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The overlooked greatwall: a new perspective on mitotic control.
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1999,
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1998,
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,
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,
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,
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,
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Suppression of scant identifies Endos as a substrate of greatwall kinase and a negative regulator of protein phosphatase 2A in mitosis.
2011,
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Spatial positive feedback at the onset of mitosis.
2012,
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Robust mitotic entry is ensured by a latching switch.
2013,
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2009,
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,
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Characterization of the mechanisms controlling Greatwall activity.
2011,
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,
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MASTL is the human orthologue of Greatwall kinase that facilitates mitotic entry, anaphase and cytokinesis.
2010,
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,
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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
,
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Greatwall kinase: a nuclear protein required for proper chromosome condensation and mitotic progression in Drosophila.
2004,
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