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



Ankers, JM, Awais, R, Jones, NA, Boyd, J ORCID: 0000-0003-0858-7179, Ryan, S, Adamson, AD, Harper, CV, Bridge, L, Spiller, DG, Jackson, DA
et al (show 3 more authors) (2016) Dynamic NF-κb and E2F interactions control the priority and timing of inflammatory signalling and cell proliferation. eLife, 2016 (5). e10473-.

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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.

Item Type: Article
Uncontrolled Keywords: Cell Line, Humans, NF-kappa B, Signal Transduction, Cell Cycle, Cell Proliferation, E2F1 Transcription Factor, E2F4 Transcription Factor, Immunity, Innate
Depositing User: Symplectic Admin
Date Deposited: 19 Jul 2016 13:57
Last Modified: 19 Jan 2023 07:33
DOI: 10.7554/eLife.10473
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3002439