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

Autor: 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
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: eLife, Vol 5 (2016)
Druh dokumentu: article
ISSN: 2050-084X
DOI: 10.7554/eLife.10473
Popis: 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.
Databáze: Directory of Open Access Journals