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

Spiller, David G.; Ankers, John M.; Jackson, Dean A.; Jones, Nicholas A.; White, Michael R.H.; Adamson, Antony D.; Harper, Claire V.; Ankers, John M; Jones, Nicholas A; Adamson, Antony D; Harper, Claire V; Awais, Raheela; Spiller, David G; Jackson, Dean A; Boyd, James; Ryan, Sheila; White, Michael RH; Bridge, Lloyd; Paszek, Pawel; S�e, Violaine

Authors

David G. Spiller

John M. Ankers

Dean A. Jackson

Nicholas A. Jones

Michael R.H. White

Antony D. Adamson

Claire V. Harper

John M Ankers

Nicholas A Jones

Antony D Adamson

Claire V Harper

Raheela Awais

David G Spiller

Dean A Jackson

James Boyd

Sheila Ryan

Michael RH White

Lloyd Bridge Lloyd.Bridge@uwe.ac.uk
Senior Lecturer in Mathematics

Pawel Paszek

Violaine S�e



Abstract

© Ankers et al. 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.

Citation

Harper, C. V., Adamson, A. D., White, M. R., Jones, N. A., Jackson, D. A., Ankers, J. M., …White, M. R. (2016). Dynamic NF-κb and E2F interactions control the priority and timing of inflammatory signalling and cell proliferation. eLife, 5(MAY2016), https://doi.org/10.7554/eLife.10473

Journal Article Type Article
Acceptance Date Apr 13, 2016
Publication Date May 17, 2016
Journal eLife
Electronic ISSN 2050-084X
Publisher eLife Sciences Publications
Peer Reviewed Peer Reviewed
Volume 5
Issue MAY2016
DOI https://doi.org/10.7554/eLife.10473
Public URL https://uwe-repository.worktribe.com/output/916426
Publisher URL http://dx.doi.org/10.7554/eLife.10473