Cell cycle regulation by feed‐forward loops coupling transcription and phosphorylation

Abstract The eukaryotic cell cycle requires precise temporal coordination of the activities of hundreds of ‘executor’ proteins (EPs) involved in cell growth and division. Cyclin‐dependent protein kinases (Cdks) play central roles in regulating the production, activation, inactivation and destruction...

Full description

Saved in:
Bibliographic Details
Main Authors: Attila Csikász‐Nagy, Orsolya Kapuy, Attila Tóth, Csaba Pál, Lars Juhl Jensen, Frank Uhlmann, John J Tyson, Béla Novák
Format: Article
Language:English
Published: Springer Nature 2009-01-01
Series:Molecular Systems Biology
Subjects:
Online Access:https://doi.org/10.1038/msb.2008.73
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849225792290029568
author Attila Csikász‐Nagy
Orsolya Kapuy
Attila Tóth
Csaba Pál
Lars Juhl Jensen
Frank Uhlmann
John J Tyson
Béla Novák
author_facet Attila Csikász‐Nagy
Orsolya Kapuy
Attila Tóth
Csaba Pál
Lars Juhl Jensen
Frank Uhlmann
John J Tyson
Béla Novák
author_sort Attila Csikász‐Nagy
collection DOAJ
description Abstract The eukaryotic cell cycle requires precise temporal coordination of the activities of hundreds of ‘executor’ proteins (EPs) involved in cell growth and division. Cyclin‐dependent protein kinases (Cdks) play central roles in regulating the production, activation, inactivation and destruction of these EPs. From genome‐scale data sets of budding yeast, we identify 126 EPs that are regulated by Cdk1 both through direct phosphorylation of the EP and through phosphorylation of the transcription factors that control expression of the EP, so that each of these EPs is regulated by a feed‐forward loop (FFL) from Cdk1. By mathematical modelling, we show that such FFLs can activate EPs at different phases of the cell cycle depending of the effective signs (+ or −) of the regulatory steps of the FFL. We provide several case studies of EPs that are controlled by FFLs exactly as our models predict. The signal‐transduction properties of FFLs allow one (or a few) Cdk signal(s) to drive a host of cell cycle responses in correct temporal sequence.
format Article
id doaj-art-c1548606fc2b40a9a971f5d61d328bf0
institution Kabale University
issn 1744-4292
language English
publishDate 2009-01-01
publisher Springer Nature
record_format Article
series Molecular Systems Biology
spelling doaj-art-c1548606fc2b40a9a971f5d61d328bf02025-08-24T11:59:38ZengSpringer NatureMolecular Systems Biology1744-42922009-01-01511610.1038/msb.2008.73Cell cycle regulation by feed‐forward loops coupling transcription and phosphorylationAttila Csikász‐Nagy0Orsolya Kapuy1Attila Tóth2Csaba Pál3Lars Juhl Jensen4Frank Uhlmann5John J Tyson6Béla Novák7The Microsoft Research––University of Trento Centre for Computational and Systems BiologyDepartment of Biochemistry, Oxford Centre for Integrative Systems Biology, University of OxfordDepartment of Applied Biotechnology and Food Science, Budapest University of Technology and EconomicsThe Microsoft Research––University of Trento Centre for Computational and Systems BiologyEuropean Molecular Biology LaboratoryChromosome Segregation Laboratory, Cancer Research UK London Research InstituteDepartment of Biological Sciences and Virginia Bioinformatics Institute, Virginia Polytechnic Institute & State UniversityDepartment of Biochemistry, Oxford Centre for Integrative Systems Biology, University of OxfordAbstract The eukaryotic cell cycle requires precise temporal coordination of the activities of hundreds of ‘executor’ proteins (EPs) involved in cell growth and division. Cyclin‐dependent protein kinases (Cdks) play central roles in regulating the production, activation, inactivation and destruction of these EPs. From genome‐scale data sets of budding yeast, we identify 126 EPs that are regulated by Cdk1 both through direct phosphorylation of the EP and through phosphorylation of the transcription factors that control expression of the EP, so that each of these EPs is regulated by a feed‐forward loop (FFL) from Cdk1. By mathematical modelling, we show that such FFLs can activate EPs at different phases of the cell cycle depending of the effective signs (+ or −) of the regulatory steps of the FFL. We provide several case studies of EPs that are controlled by FFLs exactly as our models predict. The signal‐transduction properties of FFLs allow one (or a few) Cdk signal(s) to drive a host of cell cycle responses in correct temporal sequence.https://doi.org/10.1038/msb.2008.73budding yeastcell cycleDNA replicationfeed‐forward loop
spellingShingle Attila Csikász‐Nagy
Orsolya Kapuy
Attila Tóth
Csaba Pál
Lars Juhl Jensen
Frank Uhlmann
John J Tyson
Béla Novák
Cell cycle regulation by feed‐forward loops coupling transcription and phosphorylation
Molecular Systems Biology
budding yeast
cell cycle
DNA replication
feed‐forward loop
title Cell cycle regulation by feed‐forward loops coupling transcription and phosphorylation
title_full Cell cycle regulation by feed‐forward loops coupling transcription and phosphorylation
title_fullStr Cell cycle regulation by feed‐forward loops coupling transcription and phosphorylation
title_full_unstemmed Cell cycle regulation by feed‐forward loops coupling transcription and phosphorylation
title_short Cell cycle regulation by feed‐forward loops coupling transcription and phosphorylation
title_sort cell cycle regulation by feed forward loops coupling transcription and phosphorylation
topic budding yeast
cell cycle
DNA replication
feed‐forward loop
url https://doi.org/10.1038/msb.2008.73
work_keys_str_mv AT attilacsikasznagy cellcycleregulationbyfeedforwardloopscouplingtranscriptionandphosphorylation
AT orsolyakapuy cellcycleregulationbyfeedforwardloopscouplingtranscriptionandphosphorylation
AT attilatoth cellcycleregulationbyfeedforwardloopscouplingtranscriptionandphosphorylation
AT csabapal cellcycleregulationbyfeedforwardloopscouplingtranscriptionandphosphorylation
AT larsjuhljensen cellcycleregulationbyfeedforwardloopscouplingtranscriptionandphosphorylation
AT frankuhlmann cellcycleregulationbyfeedforwardloopscouplingtranscriptionandphosphorylation
AT johnjtyson cellcycleregulationbyfeedforwardloopscouplingtranscriptionandphosphorylation
AT belanovak cellcycleregulationbyfeedforwardloopscouplingtranscriptionandphosphorylation