title: Network calisthenics: control of E2F dynamics in cell cycle entry.
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.
authors: Department of Biomedical Engineering, Institute for Genome Sciences and Policy, Duke University, Durham, NC, USA. jeff.wong@duke.edu
authors: Jeffrey V
authors: JV
authors: Wong
authors: Peng
authors: P
authors: Dong
authors: Joseph R
authors: JR
authors: Nevins
authors: Bernard
authors: B
authors: Mathey-Prevot
authors: Lingchong
authors: L
authors: You
mesh_terms: D000818:Animals; D001665:Binding Sites; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D019925:Cyclin A / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004261:DNA Replication; D050684:E2F Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008322:Mammals; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D018741:Replication Origin; D050720:Retinoblastoma-Like Protein p107 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D018797:Cell Cycle Proteins; D019925:Cyclin A; D050684:E2F Transcription Factors; C524941:MIRN17 microRNA, human; C489427:MYC protein, human; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc; C493844:RBL1 protein, human; D050720:Retinoblastoma-Like Protein p107