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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...

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Autores principales: Hached, Khaled, Goguet, Perrine, Charrasse, Sophie, Vigneron, Suzanne, Sacristan, Maria P., Lorca, Thierry, Castro, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2019
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.
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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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