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

Author

Listed:
  • Peng Dong

    (Computational Biology and Bioinformatics Program, Duke University)

  • Manoj V. Maddali

    (Duke University
    Present address: School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA)

  • Jaydeep K. Srimani

    (Duke University)

  • François Thélot

    (Duke University)

  • Joseph R. Nevins

    (Duke University)

  • Bernard Mathey-Prevot

    (Duke University
    Duke University)

  • Lingchong You

    (Duke University
    Center for Genomic and Computational Biology, Duke University
    Duke Center for Systems Biology, Duke University)

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.

Suggested Citation

  • Peng Dong & Manoj V. Maddali & Jaydeep K. Srimani & François Thélot & Joseph R. Nevins & Bernard Mathey-Prevot & Lingchong You, 2014. "Division of labour between Myc and G1 cyclins in cell cycle commitment and pace control," Nature Communications, Nature, vol. 5(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5750
    DOI: 10.1038/ncomms5750
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    Cited by:

    1. Nishtha Pandey & P K Vinod, 2018. "Mathematical modelling of reversible transition between quiescence and proliferation," PLOS ONE, Public Library of Science, vol. 13(6), pages 1-15, June.

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