Cargando…

Fcp1 phosphatase controls Greatwall kinase to promote PP2A-B55 activation and mitotic progression

During cell division, progression through mitosis is driven by a protein phosphorylation wave. This wave namely depends on an activation-inactivation cycle of cyclin B-dependent kinase (Cdk) 1 while activities of major protein phosphatases, like PP1 and PP2A, appear directly or indirectly repressed...

Descripción completa

Detalles Bibliográficos
Autores principales: Della Monica, Rosa, Visconti, Roberta, Cervone, Nando, Serpico, Angela Flavia, Grieco, Domenico
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4749544/
https://www.ncbi.nlm.nih.gov/pubmed/26653855
http://dx.doi.org/10.7554/eLife.10399
_version_ 1782415284022280192
author Della Monica, Rosa
Visconti, Roberta
Cervone, Nando
Serpico, Angela Flavia
Grieco, Domenico
author_facet Della Monica, Rosa
Visconti, Roberta
Cervone, Nando
Serpico, Angela Flavia
Grieco, Domenico
author_sort Della Monica, Rosa
collection PubMed
description During cell division, progression through mitosis is driven by a protein phosphorylation wave. This wave namely depends on an activation-inactivation cycle of cyclin B-dependent kinase (Cdk) 1 while activities of major protein phosphatases, like PP1 and PP2A, appear directly or indirectly repressed by Cdk1. However, how Cdk1 inactivation is coordinated with reactivation of major phosphatases at mitosis exit still lacks substantial knowledge. We show here that activation of PP2A-B55, a major mitosis exit phosphatase, required the phosphatase Fcp1 downstream Cdk1 inactivation in human cells. During mitosis exit, Fcp1 bound Greatwall (Gwl), a Cdk1-stimulated kinase that phosphorylates Ensa/ARPP19 and converts these proteins into potent PP2A-B55 inhibitors during mitosis onset, and dephosphorylated it at Cdk1 phosphorylation sites. Fcp1-catalyzed dephosphorylation drastically reduced Gwl kinase activity towards Ensa/ARPP19 promoting PP2A-B55 activation. Thus, Fcp1 coordinates Cdk1 and Gwl inactivation to derepress PP2A-B55, generating a dephosphorylation switch that drives mitosis progression. DOI: http://dx.doi.org/10.7554/eLife.10399.001
format Online
Article
Text
id pubmed-4749544
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher eLife Sciences Publications, Ltd
record_format MEDLINE/PubMed
spelling pubmed-47495442016-02-12 Fcp1 phosphatase controls Greatwall kinase to promote PP2A-B55 activation and mitotic progression Della Monica, Rosa Visconti, Roberta Cervone, Nando Serpico, Angela Flavia Grieco, Domenico eLife Cell Biology During cell division, progression through mitosis is driven by a protein phosphorylation wave. This wave namely depends on an activation-inactivation cycle of cyclin B-dependent kinase (Cdk) 1 while activities of major protein phosphatases, like PP1 and PP2A, appear directly or indirectly repressed by Cdk1. However, how Cdk1 inactivation is coordinated with reactivation of major phosphatases at mitosis exit still lacks substantial knowledge. We show here that activation of PP2A-B55, a major mitosis exit phosphatase, required the phosphatase Fcp1 downstream Cdk1 inactivation in human cells. During mitosis exit, Fcp1 bound Greatwall (Gwl), a Cdk1-stimulated kinase that phosphorylates Ensa/ARPP19 and converts these proteins into potent PP2A-B55 inhibitors during mitosis onset, and dephosphorylated it at Cdk1 phosphorylation sites. Fcp1-catalyzed dephosphorylation drastically reduced Gwl kinase activity towards Ensa/ARPP19 promoting PP2A-B55 activation. Thus, Fcp1 coordinates Cdk1 and Gwl inactivation to derepress PP2A-B55, generating a dephosphorylation switch that drives mitosis progression. DOI: http://dx.doi.org/10.7554/eLife.10399.001 eLife Sciences Publications, Ltd 2015-12-14 /pmc/articles/PMC4749544/ /pubmed/26653855 http://dx.doi.org/10.7554/eLife.10399 Text en © 2015, Della Monica et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Della Monica, Rosa
Visconti, Roberta
Cervone, Nando
Serpico, Angela Flavia
Grieco, Domenico
Fcp1 phosphatase controls Greatwall kinase to promote PP2A-B55 activation and mitotic progression
title Fcp1 phosphatase controls Greatwall kinase to promote PP2A-B55 activation and mitotic progression
title_full Fcp1 phosphatase controls Greatwall kinase to promote PP2A-B55 activation and mitotic progression
title_fullStr Fcp1 phosphatase controls Greatwall kinase to promote PP2A-B55 activation and mitotic progression
title_full_unstemmed Fcp1 phosphatase controls Greatwall kinase to promote PP2A-B55 activation and mitotic progression
title_short Fcp1 phosphatase controls Greatwall kinase to promote PP2A-B55 activation and mitotic progression
title_sort fcp1 phosphatase controls greatwall kinase to promote pp2a-b55 activation and mitotic progression
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4749544/
https://www.ncbi.nlm.nih.gov/pubmed/26653855
http://dx.doi.org/10.7554/eLife.10399
work_keys_str_mv AT dellamonicarosa fcp1phosphatasecontrolsgreatwallkinasetopromotepp2ab55activationandmitoticprogression
AT viscontiroberta fcp1phosphatasecontrolsgreatwallkinasetopromotepp2ab55activationandmitoticprogression
AT cervonenando fcp1phosphatasecontrolsgreatwallkinasetopromotepp2ab55activationandmitoticprogression
AT serpicoangelaflavia fcp1phosphatasecontrolsgreatwallkinasetopromotepp2ab55activationandmitoticprogression
AT griecodomenico fcp1phosphatasecontrolsgreatwallkinasetopromotepp2ab55activationandmitoticprogression