Network calisthenics: Control of E2F dynamics in cell cycle entry |
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| Authors: | Jeffrey V Wong Peng Dong Joseph R Nevins Bernard Mathey-Prevot Lingchong You |
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| Affiliation: | 1.Department of Biomedical Engineering; Duke University; Durham, NC USA;2.Institute for Genome Sciences and Policy; Duke University; Durham, NC USA;3.Computational Biology and Bioinformatics Program; Duke University; Durham, NC USA;4.Department of Molecular Genetics and Microbiology; Duke University; Durham, NC USA;5.Deparment of Pharmacology & Cancer Biology; Duke University; Durham, NC USA;6.Duke Center for Systems Biology; Duke University; Durham, NC USA |
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| Abstract: | Stimulation of quiescent mammalian cells with mitogens induces an abrupt increase in E2F1–3 expression just prior to the onset of DNA synthesis, followed by a rapid decline as replication ceases. This temporal adaptation in E2F facilitates a transient pattern of gene expression that reflects the ordered nature of DNA replication. The challenge to understand how E2F dynamics coordinate molecular events required for high-fidelity DNA replication has great biological implications. Indeed, precocious, prolonged, elevated or reduced accumulation of E2F can generate replication stress that culminates in either arrest or death. Accordingly, temporal characteristics of E2F are regulated by several network modules that include feedforward and autoregulatory loops. In this review, we discuss how these network modules contribute to “shaping” E2F dynamics in the context of mammalian cell cycle entry.Key words: E2F, dynamics, feedback, feedforward, network, DNA replication |
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