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

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.

动态细胞系统通过重编程基因表达，确保细胞对特定细胞外信号产生恰当的细胞命运应答。本研究证实，核因子κB（Nuclear Factor kappa B, NF-κB）信号通路与细胞周期的动态变化，会根据炎症信号的触发时机被差异化优先调控。通过迭代式实验与计算分析，我们发现NF-κB与细胞周期调控因子E2因子1（E2 Factor 1, E2F-1）、E2因子4（E2 Factor 4, E2F-4）之间存在物理与功能相互作用，且此类相互作用可调控NF-κB的应答过程。在S期，NF-κB的应答会被延迟或抑制，而细胞周期进程则不受阻碍；与之相反，若在G1/S期交界激活NF-κB，则会导致细胞周期时长增加，且细胞间初始NF-κB应答的同步性更高。本研究的数据揭示了全新的调控机制：细胞对应激的应答会在细胞周期的不同阶段被差异化调控。