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Nat Commun. 2014 Sep 1;5:4750. doi: 10.1038/ncomms5750.

Division of labour between Myc and G1 cyclins in cell cycle commitment and pace control.

Author information

1
Computational Biology and Bioinformatics Program, Duke University, Durham, North Carolina 27708, USA.
2
1] Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708, USA [2].
3
Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708, USA.
4
Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina 27708, USA.
5
Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina 27708, USA.
6
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.
7
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.

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.

PMID:
25175461
PMCID:
PMC4164785
DOI:
10.1038/ncomms5750
[Indexed for MEDLINE]
Free PMC Article

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