Dynamic NF-κB and E2F interactions control the priority and timing of inflammatory signalling and cell proliferation
Open Access
- 17 May 2016
- journal article
- research article
- Published by eLife Sciences Publications, Ltd in eLife
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.Keywords
Funding Information
- Biotechnology and Biological Sciences Research Council (BBH0137252)
- Biotechnology and Biological Sciences Research Council (BBF5290031)
- Medical Research Council (G0500346)
- Professor John Glover Memorial Fellowship (N/A)
- Biotechnology and Biological Sciences Research Council (BB/K003097/1)
- Medical Research Council (MR/K015885/1)
- Biotechnology and Biological Sciences Research Council (BBF0059382/BBF00561X1)
- Biotechnology and Biological Sciences Research Council (BBI0179761)
- Biotechnology and Biological Sciences Research Council (BBC5204711)
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