4.6 Article

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

期刊

MOLECULAR SYSTEMS BIOLOGY
卷 5, 期 -, 页码 -

出版社

NATURE PUBLISHING GROUP
DOI: 10.1038/msb.2008.73

关键词

budding yeast; cell cycle; DNA replication; feed-forward loop

资金

  1. Hungarian Scientific Research Fund [OTKA-F60414]
  2. Italian Ministry of University and Research Project FIRB [RBPR0523C3]
  3. European Research Council [202591]
  4. European Commission [FP7: 201142]
  5. National Institutes of Health [5R01GM079207]
  6. James S McDonnell Foundation [21002050]
  7. NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM079207] Funding Source: NIH RePORTER

向作者/读者索取更多资源

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.

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