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...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2009-01-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.1038/msb.2008.73 |
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| _version_ | 1849225792290029568 |
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| 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 |
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