ArticleThe Journal of cell biology2021
Spatiotemporal coordination of Greatwall-Endos-PP2A promotes mitotic progression.
Article in The Journal of cell biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 6 citations in OpenAlex.
- Greatwall-Endos-PP2A/B55Open biology · 2024Article
- Identification of PP2A-B55 targets uncovers regulation of emerin during nuclear envelope reassembly inOpen biology · 2023Article
- CDC6 as a Key Inhibitory Regulator of CDK1 Activation Dynamics and the Timing of Mitotic Entry and Progression.Biology · 2023Review
- Therapeutic natural compounds Enzastaurin and Palbociclib inhibit MASTL kinase activity preventing breast cancer cell proliferation.Medical oncology (Northwood, London, England) · 2022Article
- Structural, enzymatic and spatiotemporal regulation of PP2A-B55 phosphatase in the control of mitosis.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Mitotic entry involves inhibition of protein phosphatase 2A bound to its B55/Tws regulatory subunit (PP2A-B55/Tws), which dephosphorylates substrates of mitotic kinases. This inhibition is induced when Greatwall phosphorylates Endos, turning it into an inhibitor of PP2A-Tws. How this mechanism operates spatiotemporally in the cell is incompletely understood. We previously reported that the nuclear export of Greatwall in prophase promotes mitotic progression. Here, we examine the importance of the localized activities of PP2A-Tws and Endos for mitotic regulation. We find that Tws shuttles through the nucleus via a conserved nuclear localization signal (NLS), but expression of Tws in the cytoplasm and not in the nucleus rescues the development of tws mutants. Moreover, we show that Endos must be in the cytoplasm before nuclear envelope breakdown (NEBD) to be efficiently phosphorylated by Greatwall and to bind and inhibit PP2A-Tws. Disrupting the cytoplasmic function of Endos before NEBD results in subsequent mitotic defects. Evidence suggests that this spatiotemporal regulation is conserved in humans.
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Registered trials
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