Dynamic NF-κB and E2F interactions control the priority and timing of inflammatory signalling and cell proliferation

John M Ankers, Raheela Awais, Nicholas A Jones, James Boyd, Sheila Ryan, Antony D Adamson, Claire V Harper, Lloyd Bridge, David G Spiller, Dean A Jackson, Pawel Paszek, Violaine Sée, Michael Rh White

Research output: Contribution to journalArticle

17 Citations (Scopus)
31 Downloads (Pure)

Abstract

Dynamic cellular systems reprogram gene expression to ensure appropriate cellular fate responses to specific extracellular cues. Here we demonstrate that the dynamics of Nuclear Factor kappa B (NF-κB) signalling and the cell cycle are prioritised differently depending on the timing of an inflammatory signal. Using iterative experimental and computational analyses, we show physical and functional interactions between NF-κB and the E2 Factor 1 (E2F-1) and E2 Factor 4 (E2F-4) cell cycle regulators. These interactions modulate the NF-κB response. In S-phase, the NF-κB response was delayed or repressed, while cell cycle progression was unimpeded. By contrast, activation of NF-κB at the G1/S boundary resulted in a longer cell cycle and more synchronous initial NF-κB responses between cells. These data identify new mechanisms by which the cellular response to stress is differentially controlled at different stages of the cell cycle.

Original languageEnglish
JournaleLife
Volume5
Early online date17 May 2016
DOIs
Publication statusPublished - 17 May 2016

Keywords

  • Cell Cycle
  • Cell Line
  • Cell Proliferation
  • E2F1 Transcription Factor/metabolism
  • E2F4 Transcription Factor/metabolism
  • Humans
  • Immunity, Innate
  • NF-kappa B/metabolism
  • Signal Transduction

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    Ankers, J. M., Awais, R., Jones, N. A., Boyd, J., Ryan, S., Adamson, A. D., Harper, C. V., Bridge, L., Spiller, D. G., Jackson, D. A., Paszek, P., Sée, V., & White, M. R. (2016). Dynamic NF-κB and E2F interactions control the priority and timing of inflammatory signalling and cell proliferation. eLife, 5. https://doi.org/10.7554/eLife.10473