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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Minimal model of spiky oscillations in NF-kappa B signaling
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Minimal model of spiky oscillations in NF-kappa B signaling

机译：NF-κB信号传导中尖峰振荡的最小模型

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The NF-kappa B signaling system is involved in a variety of cellular processes including immune response, inflammation, and apoptosis. Recent experiments have found oscillations in the nuclearcytoplasmic translocation of the NF-kappa B transcription factor [Hoffmann, A., et al. (2002) Science 298, 1241-1245; Nelson, D. E., et al. (2004) Science 306, 704-708.] How the cell uses the oscillations to differentiate input conditions and send specific signals to downstream genes is an open problem. We shed light on this issue by examining the small core network driving the oscillations, which we show is designed to produce periodic spikes in nuclear NF-KB concentration. The presence of oscillations is extremely robust to variation of parameters, depending mainly on the saturation of the active degradation rate of I kappa B, an inhibitor of NF-KB. The oscillations can be used to regulate downstream genes in a variety of ways. In particular, we show that genes to whose operator sites NF-KB binds and dissociates fast can respond very sensitively to changes in the input signal, with effective Hill coefficients of > 20.
机译：NF-κB信号系统参与多种细胞过程，包括免疫反应，炎症和凋亡。最近的实验已经发现NF-κB转录因子在核质​​易位中的振荡[Hoffmann，A。等人。 （2002）Science 298，1241-1245； Nelson，D. E.等。 （2004）Science 306，704-708。]细胞如何利用振荡来区分输入条件并向下游基因发送特定信号是一个悬而未决的问题。通过研究驱动振荡的小型核心网络，我们揭示了这个问题，我们证明该网络设计用于产生核NF-KB浓度的周期性峰值。振荡的存在对于参数的变化极其鲁棒，主要取决于NF-KB抑制剂IκB的活性降解速率的饱和度。振荡可以以多种方式用于调节下游基因。特别是，我们证明了其操纵子位点NF-KB能够快速结合和解离的基因可以非常敏感地响应输入信号的变化，有效Hill系数> 20。

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