title: Division of labour between Myc and G1 cyclins in cell cycle commitment and pace control.
abstract: A body of evidence has shown that the control of E2F transcription factor activity is critical for determining cell cycle entry and cell proliferation. However, an understanding of the precise determinants of this control, including the role of other cell-cycle regulatory activities, has not been clearly defined. Here, recognizing that the contributions of individual regulatory components could be masked by heterogeneity in populations of cells, we model the potential roles of individual components together with the use of an integrated system to follow E2F dynamics at the single-cell level and in real time. These analyses reveal that crossing a threshold amplitude of E2F accumulation determines cell cycle commitment. Importantly, we find that Myc is critical in modulating the amplitude, whereas cyclin D/E activities have little effect on amplitude but do contribute to the modulation of duration of E2F activation, thereby affecting the pace of cell cycle progression.
authors.affiliation: Computational Biology and Bioinformatics Program, Duke University, Durham, North Carolina 27708, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Dong
authors.affiliation: 1] Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708, USA [2].
authors.forename: Manoj V
authors.initials: MV
authors.lastname: Maddali
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708, USA.
authors.forename: Jaydeep K
authors.initials: JK
authors.lastname: Srimani
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina 27708, USA.
authors.forename: François
authors.initials: F
authors.lastname: Thélot
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina 27708, USA.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Nevins
authors.affiliation: 1] Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina 27708, USA [2] Department of Pediatrics, Duke University, Durham, North Carolina 27708, USA.
authors.forename: Bernard
authors.initials: B
authors.lastname: Mathey-Prevot
authors.affiliation: 1] Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708, USA [2] Center for Genomic and Computational Biology, Duke University, Durham, North Carolina 27708, USA [3] Duke Center for Systems Biology, Duke University, Durham, North Carolina 27708, USA.
authors.forename: Lingchong
authors.initials: L
authors.lastname: You
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics*; D002460:Cell Line; D056741:Cyclin D / Q000235:genetics* / Q000378:metabolism; D019927:Cyclin E / Q000235:genetics* / Q000378:metabolism; D050687:E2F1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D010879:Piperazines / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D011687:Purines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction; D059010:Single-Cell Analysis; D059008:Time-Lapse Imaging
chemical_list: D001426:Bacterial Proteins; D056741:Cyclin D; D019927:Cyclin E; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D008164:Luminescent Proteins; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D016271:Proto-Oncogene Proteins c-myc; D011687:Purines; D011725:Pyridines; C054562:yellow fluorescent protein, Bacteria; C500026:palbociclib; C109140:CVT 313