Cargando…

A Clb/Cdk1-mediated regulation of Fkh2 synchronizes CLB expression in the budding yeast cell cycle

Precise timing of cell division is achieved by coupling waves of cyclin-dependent kinase (Cdk) activity with a transcriptional oscillator throughout cell cycle progression. Although details of transcription of cyclin genes are known, it is unclear which is the transcriptional cascade that modulates...

Descripción completa

Detalles Bibliográficos
Autores principales: Linke, Christian, Chasapi, Anastasia, González-Novo, Alberto, Al Sawad, Istabrak, Tognetti, Silvia, Klipp, Edda, Loog, Mart, Krobitsch, Sylvia, Posas, Francesc, Xenarios, Ioannis, Barberis, Matteo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5460246/
https://www.ncbi.nlm.nih.gov/pubmed/28649434
http://dx.doi.org/10.1038/s41540-017-0008-1
_version_ 1783242127004663808
author Linke, Christian
Chasapi, Anastasia
González-Novo, Alberto
Al Sawad, Istabrak
Tognetti, Silvia
Klipp, Edda
Loog, Mart
Krobitsch, Sylvia
Posas, Francesc
Xenarios, Ioannis
Barberis, Matteo
author_facet Linke, Christian
Chasapi, Anastasia
González-Novo, Alberto
Al Sawad, Istabrak
Tognetti, Silvia
Klipp, Edda
Loog, Mart
Krobitsch, Sylvia
Posas, Francesc
Xenarios, Ioannis
Barberis, Matteo
author_sort Linke, Christian
collection PubMed
description Precise timing of cell division is achieved by coupling waves of cyclin-dependent kinase (Cdk) activity with a transcriptional oscillator throughout cell cycle progression. Although details of transcription of cyclin genes are known, it is unclear which is the transcriptional cascade that modulates their expression in a timely fashion. Here, we demonstrate that a Clb/Cdk1-mediated regulation of the Fkh2 transcription factor synchronizes the temporal mitotic CLB expression in budding yeast. A simplified kinetic model of the cyclin/Cdk network predicts a linear cascade where a Clb/Cdk1-mediated regulation of an activator molecule drives CLB3 and CLB2 expression. Experimental validation highlights Fkh2 as modulator of CLB3 transcript levels, besides its role in regulating CLB2 expression. A Boolean model based on the minimal number of interactions needed to capture the information flow of the Clb/Cdk1 network supports the role of an activator molecule in the sequential activation, and oscillatory behavior, of mitotic Clb cyclins. This work illustrates how transcription and phosphorylation networks can be coupled by a Clb/Cdk1-mediated regulation that synchronizes them.
format Online
Article
Text
id pubmed-5460246
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-54602462017-06-23 A Clb/Cdk1-mediated regulation of Fkh2 synchronizes CLB expression in the budding yeast cell cycle Linke, Christian Chasapi, Anastasia González-Novo, Alberto Al Sawad, Istabrak Tognetti, Silvia Klipp, Edda Loog, Mart Krobitsch, Sylvia Posas, Francesc Xenarios, Ioannis Barberis, Matteo NPJ Syst Biol Appl Article Precise timing of cell division is achieved by coupling waves of cyclin-dependent kinase (Cdk) activity with a transcriptional oscillator throughout cell cycle progression. Although details of transcription of cyclin genes are known, it is unclear which is the transcriptional cascade that modulates their expression in a timely fashion. Here, we demonstrate that a Clb/Cdk1-mediated regulation of the Fkh2 transcription factor synchronizes the temporal mitotic CLB expression in budding yeast. A simplified kinetic model of the cyclin/Cdk network predicts a linear cascade where a Clb/Cdk1-mediated regulation of an activator molecule drives CLB3 and CLB2 expression. Experimental validation highlights Fkh2 as modulator of CLB3 transcript levels, besides its role in regulating CLB2 expression. A Boolean model based on the minimal number of interactions needed to capture the information flow of the Clb/Cdk1 network supports the role of an activator molecule in the sequential activation, and oscillatory behavior, of mitotic Clb cyclins. This work illustrates how transcription and phosphorylation networks can be coupled by a Clb/Cdk1-mediated regulation that synchronizes them. Nature Publishing Group UK 2017-03-06 /pmc/articles/PMC5460246/ /pubmed/28649434 http://dx.doi.org/10.1038/s41540-017-0008-1 Text en © The Author(s) 2017 This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Linke, Christian
Chasapi, Anastasia
González-Novo, Alberto
Al Sawad, Istabrak
Tognetti, Silvia
Klipp, Edda
Loog, Mart
Krobitsch, Sylvia
Posas, Francesc
Xenarios, Ioannis
Barberis, Matteo
A Clb/Cdk1-mediated regulation of Fkh2 synchronizes CLB expression in the budding yeast cell cycle
title A Clb/Cdk1-mediated regulation of Fkh2 synchronizes CLB expression in the budding yeast cell cycle
title_full A Clb/Cdk1-mediated regulation of Fkh2 synchronizes CLB expression in the budding yeast cell cycle
title_fullStr A Clb/Cdk1-mediated regulation of Fkh2 synchronizes CLB expression in the budding yeast cell cycle
title_full_unstemmed A Clb/Cdk1-mediated regulation of Fkh2 synchronizes CLB expression in the budding yeast cell cycle
title_short A Clb/Cdk1-mediated regulation of Fkh2 synchronizes CLB expression in the budding yeast cell cycle
title_sort clb/cdk1-mediated regulation of fkh2 synchronizes clb expression in the budding yeast cell cycle
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5460246/
https://www.ncbi.nlm.nih.gov/pubmed/28649434
http://dx.doi.org/10.1038/s41540-017-0008-1
work_keys_str_mv AT linkechristian aclbcdk1mediatedregulationoffkh2synchronizesclbexpressioninthebuddingyeastcellcycle
AT chasapianastasia aclbcdk1mediatedregulationoffkh2synchronizesclbexpressioninthebuddingyeastcellcycle
AT gonzaleznovoalberto aclbcdk1mediatedregulationoffkh2synchronizesclbexpressioninthebuddingyeastcellcycle
AT alsawadistabrak aclbcdk1mediatedregulationoffkh2synchronizesclbexpressioninthebuddingyeastcellcycle
AT tognettisilvia aclbcdk1mediatedregulationoffkh2synchronizesclbexpressioninthebuddingyeastcellcycle
AT klippedda aclbcdk1mediatedregulationoffkh2synchronizesclbexpressioninthebuddingyeastcellcycle
AT loogmart aclbcdk1mediatedregulationoffkh2synchronizesclbexpressioninthebuddingyeastcellcycle
AT krobitschsylvia aclbcdk1mediatedregulationoffkh2synchronizesclbexpressioninthebuddingyeastcellcycle
AT posasfrancesc aclbcdk1mediatedregulationoffkh2synchronizesclbexpressioninthebuddingyeastcellcycle
AT xenariosioannis aclbcdk1mediatedregulationoffkh2synchronizesclbexpressioninthebuddingyeastcellcycle
AT barberismatteo aclbcdk1mediatedregulationoffkh2synchronizesclbexpressioninthebuddingyeastcellcycle
AT linkechristian clbcdk1mediatedregulationoffkh2synchronizesclbexpressioninthebuddingyeastcellcycle
AT chasapianastasia clbcdk1mediatedregulationoffkh2synchronizesclbexpressioninthebuddingyeastcellcycle
AT gonzaleznovoalberto clbcdk1mediatedregulationoffkh2synchronizesclbexpressioninthebuddingyeastcellcycle
AT alsawadistabrak clbcdk1mediatedregulationoffkh2synchronizesclbexpressioninthebuddingyeastcellcycle
AT tognettisilvia clbcdk1mediatedregulationoffkh2synchronizesclbexpressioninthebuddingyeastcellcycle
AT klippedda clbcdk1mediatedregulationoffkh2synchronizesclbexpressioninthebuddingyeastcellcycle
AT loogmart clbcdk1mediatedregulationoffkh2synchronizesclbexpressioninthebuddingyeastcellcycle
AT krobitschsylvia clbcdk1mediatedregulationoffkh2synchronizesclbexpressioninthebuddingyeastcellcycle
AT posasfrancesc clbcdk1mediatedregulationoffkh2synchronizesclbexpressioninthebuddingyeastcellcycle
AT xenariosioannis clbcdk1mediatedregulationoffkh2synchronizesclbexpressioninthebuddingyeastcellcycle
AT barberismatteo clbcdk1mediatedregulationoffkh2synchronizesclbexpressioninthebuddingyeastcellcycle