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

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.

• 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