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Spatiotemporal coordination of Greatwall-Endos-PP2A promotes mitotic progression
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 opera...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042607/ https://www.ncbi.nlm.nih.gov/pubmed/33836042 http://dx.doi.org/10.1083/jcb.202008145 |
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author | Larouche, Myreille Kachaner, David Wang, Peng Normandin, Karine Garrido, Damien Yao, Changfu Cormier, Maxime Johansen, Kristen M. Johansen, Jørgen Archambault, Vincent |
author_facet | Larouche, Myreille Kachaner, David Wang, Peng Normandin, Karine Garrido, Damien Yao, Changfu Cormier, Maxime Johansen, Kristen M. Johansen, Jørgen Archambault, Vincent |
author_sort | Larouche, Myreille |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8042607 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-80426072021-12-07 Spatiotemporal coordination of Greatwall-Endos-PP2A promotes mitotic progression Larouche, Myreille Kachaner, David Wang, Peng Normandin, Karine Garrido, Damien Yao, Changfu Cormier, Maxime Johansen, Kristen M. Johansen, Jørgen Archambault, Vincent J Cell Biol Article 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. Rockefeller University Press 2021-04-09 /pmc/articles/PMC8042607/ /pubmed/33836042 http://dx.doi.org/10.1083/jcb.202008145 Text en © 2021 Larouche et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Larouche, Myreille Kachaner, David Wang, Peng Normandin, Karine Garrido, Damien Yao, Changfu Cormier, Maxime Johansen, Kristen M. Johansen, Jørgen Archambault, Vincent Spatiotemporal coordination of Greatwall-Endos-PP2A promotes mitotic progression |
title | Spatiotemporal coordination of Greatwall-Endos-PP2A promotes mitotic progression |
title_full | Spatiotemporal coordination of Greatwall-Endos-PP2A promotes mitotic progression |
title_fullStr | Spatiotemporal coordination of Greatwall-Endos-PP2A promotes mitotic progression |
title_full_unstemmed | Spatiotemporal coordination of Greatwall-Endos-PP2A promotes mitotic progression |
title_short | Spatiotemporal coordination of Greatwall-Endos-PP2A promotes mitotic progression |
title_sort | spatiotemporal coordination of greatwall-endos-pp2a promotes mitotic progression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042607/ https://www.ncbi.nlm.nih.gov/pubmed/33836042 http://dx.doi.org/10.1083/jcb.202008145 |
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