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ENSA and ARPP19 differentially control cell cycle progression and development
Greatwall (GWL) is an essential kinase that indirectly controls PP2A-B55, the phosphatase counterbalancing cyclin B/CDK1 activity during mitosis. In Xenopus laevis egg extracts, GWL-mediated phosphorylation of overexpressed ARPP19 and ENSA turns them into potent PP2A-B55 inhibitors. It has been show...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363464/ https://www.ncbi.nlm.nih.gov/pubmed/30626720 http://dx.doi.org/10.1083/jcb.201708105 |
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author | Hached, Khaled Goguet, Perrine Charrasse, Sophie Vigneron, Suzanne Sacristan, Maria P. Lorca, Thierry Castro, Anna |
author_facet | Hached, Khaled Goguet, Perrine Charrasse, Sophie Vigneron, Suzanne Sacristan, Maria P. Lorca, Thierry Castro, Anna |
author_sort | Hached, Khaled |
collection | PubMed |
description | Greatwall (GWL) is an essential kinase that indirectly controls PP2A-B55, the phosphatase counterbalancing cyclin B/CDK1 activity during mitosis. In Xenopus laevis egg extracts, GWL-mediated phosphorylation of overexpressed ARPP19 and ENSA turns them into potent PP2A-B55 inhibitors. It has been shown that the GWL/ENSA/PP2A-B55 axis contributes to the control of DNA replication, but little is known about the role of ARPP19 in cell division. By using conditional knockout mouse models, we investigated the specific roles of ARPP19 and ENSA in cell division. We found that Arpp19, but not Ensa, is essential for mouse embryogenesis. Moreover, Arpp19 ablation dramatically decreased mouse embryonic fibroblast (MEF) viability by perturbing the temporal pattern of protein dephosphorylation during mitotic progression, possibly by a drop of PP2A-B55 activity inhibition. We show that these alterations are not prevented by ENSA, which is still expressed in Arpp19(Δ/Δ) MEFs, suggesting that ARPP19 is essential for mitotic division. Strikingly, we demonstrate that unlike ARPP19, ENSA is not required for early embryonic development. Arpp19 knockout did not perturb the S phase, unlike Ensa gene ablation. We conclude that, during mouse embryogenesis, the Arpp19 and Ensa paralog genes display specific functions by differentially controlling cell cycle progression. |
format | Online Article Text |
id | pubmed-6363464 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-63634642019-08-04 ENSA and ARPP19 differentially control cell cycle progression and development Hached, Khaled Goguet, Perrine Charrasse, Sophie Vigneron, Suzanne Sacristan, Maria P. Lorca, Thierry Castro, Anna J Cell Biol Research Articles Greatwall (GWL) is an essential kinase that indirectly controls PP2A-B55, the phosphatase counterbalancing cyclin B/CDK1 activity during mitosis. In Xenopus laevis egg extracts, GWL-mediated phosphorylation of overexpressed ARPP19 and ENSA turns them into potent PP2A-B55 inhibitors. It has been shown that the GWL/ENSA/PP2A-B55 axis contributes to the control of DNA replication, but little is known about the role of ARPP19 in cell division. By using conditional knockout mouse models, we investigated the specific roles of ARPP19 and ENSA in cell division. We found that Arpp19, but not Ensa, is essential for mouse embryogenesis. Moreover, Arpp19 ablation dramatically decreased mouse embryonic fibroblast (MEF) viability by perturbing the temporal pattern of protein dephosphorylation during mitotic progression, possibly by a drop of PP2A-B55 activity inhibition. We show that these alterations are not prevented by ENSA, which is still expressed in Arpp19(Δ/Δ) MEFs, suggesting that ARPP19 is essential for mitotic division. Strikingly, we demonstrate that unlike ARPP19, ENSA is not required for early embryonic development. Arpp19 knockout did not perturb the S phase, unlike Ensa gene ablation. We conclude that, during mouse embryogenesis, the Arpp19 and Ensa paralog genes display specific functions by differentially controlling cell cycle progression. Rockefeller University Press 2019-02-04 /pmc/articles/PMC6363464/ /pubmed/30626720 http://dx.doi.org/10.1083/jcb.201708105 Text en © 2019 Hached 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 | Research Articles Hached, Khaled Goguet, Perrine Charrasse, Sophie Vigneron, Suzanne Sacristan, Maria P. Lorca, Thierry Castro, Anna ENSA and ARPP19 differentially control cell cycle progression and development |
title | ENSA and ARPP19 differentially control cell cycle progression and development |
title_full | ENSA and ARPP19 differentially control cell cycle progression and development |
title_fullStr | ENSA and ARPP19 differentially control cell cycle progression and development |
title_full_unstemmed | ENSA and ARPP19 differentially control cell cycle progression and development |
title_short | ENSA and ARPP19 differentially control cell cycle progression and development |
title_sort | ensa and arpp19 differentially control cell cycle progression and development |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363464/ https://www.ncbi.nlm.nih.gov/pubmed/30626720 http://dx.doi.org/10.1083/jcb.201708105 |
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