核因子-κB与干扰素调节因子信号通路：靶基因启动子水平的交叉调控
NF-κB and IRF pathways: cross-regulation on target genes promoter level.
作者信息
Iwanaszko Marta, Kimmel Marek
机构信息
Systems Engineering Group, Silesian University of Technology, Gliwice, Poland.
Department of Statistics, Rice University, Houston, TX, USA.
出版信息
BMC Genomics. 2015 Apr 17;16(1):307. doi: 10.1186/s12864-015-1511-7.
BACKGROUND
The NF-κB and IRF transcription factor families are major players in inflammation and antiviral response and act as two major effectors of the innate immune response (IIR). The regulatory mechanisms of activation of these two pathways and their interactions during the IIR are only partially known.
RESULTS
Our in silico findings report that there is cross-regulation between both pathways at the level of gene transcription regulation, mediated by the presence of binding sites for both factors in promoters of genes essential for these pathways. These findings agree with recent experimental data reporting crosstalk between pathways activated by RIG-I and TLR3 receptors in response to pathogens.
CONCLUSIONS
We present an extended crosstalk diagram of the IRF - NF-κB pathways. We conclude that members of the NF-κB family may directly impact regulation of IRF family, while IRF members impact regulation of NF-κB family rather indirectly, via other transcription factors such as AP-1 and SP1.
背景
核因子κB（NF-κB）和干扰素调节因子（IRF）转录因子家族是炎症和抗病毒反应的主要参与者，也是固有免疫反应（IIR）的两个主要效应器。这两条信号通路激活的调控机制及其在IIR过程中的相互作用目前仅部分为人所知。
结果
我们的计算机模拟研究结果表明，在基因转录调控水平上，这两条信号通路之间存在交叉调控，这是由这两条信号通路必需基因启动子中两个因子的结合位点介导的。这些结果与最近的实验数据一致，这些实验数据报道了由视黄酸诱导基因I（RIG-I）和Toll样受体3（TLR3）激活的信号通路在病原体应答中的串扰。
结论
我们给出了IRF-NF-κB信号通路的扩展串扰图。我们得出结论，NF-κB家族成员可能直接影响IRF家族的调控，而IRF家族成员则通过其他转录因子如激活蛋白-1（AP-1）和特异性蛋白1（SP1）间接影响NF-κB家族的调控。
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