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首页> 外文期刊>Molecular and Cellular Biology >Fas-Associated Factor 1 Negatively Regulates the Antiviral Immune Response by Inhibiting Translocation of Interferon Regulatory Factor 3 to the Nucleus
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Fas-Associated Factor 1 Negatively Regulates the Antiviral Immune Response by Inhibiting Translocation of Interferon Regulatory Factor 3 to the Nucleus

机译:Fas相关因子1通过抑制干扰素调节因子3向核的转移来负调节抗病毒免疫反应。

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This study is designed to examine the cellular functions of human Fas-associated factor 1 (FAF1) containing multiple ubiquitin-related domains. Microarray analyses revealed that interferon-stimulated genes related to the antiviral response are significantly increased in FAF1-knockdown HeLa cells. Silencing FAF1 enhanced the poly(I·C)- and respiratory syncytial virus (RSV)-induced production of type I interferons (IFNs), the target genes of interferon regulator factor 3 (IRF3). IRF3 is a key transcription factor in IFN-β signaling responsible for the host innate immune response. This study also found that FAF1 and IRF3 physically associate with IPO5/importin-β3 and that overexpression of FAF1 reduces the interaction between IRF3 and IPO5/importin-β3. These findings suggest that FAF1 negatively regulates IRF3-mediated IFN-β production and the antiviral innate immune response by regulating nuclear translocation of IRF3. We conclude that FAF1 plays a novel role in negatively regulating virus-induced IFN-β production and the antiviral response by inhibiting the translocation of active, phosphorylated IRF3 from the cytosol to the nucleus.
机译:这项研究旨在检查包含多个泛素相关域的人类Fas相关因子1(FAF1)的细胞功能。基因芯片分析表明,FAF1抑制HeLa细胞中与抗病毒应答有关的干扰素刺激基因显着增加。沉默FAF1增强了聚(I·C)和呼吸道合胞病毒(RSV)诱导的I型干扰素(IFN)的产生,I型干扰素是干扰素调节因子3(IRF3)的靶基因。 IRF3是负责宿主固有免疫反应的IFN-β信号传导中的关键转录因子。这项研究还发现,FAF1和IRF3在物理上与IPO5 /importin-β3相关,而FAF1的过表达减少了IRF3与IPO5 /importin-β3之间的相互作用。这些发现表明,FAF1通过调节IRF3的核转运来负调节IRF3介导的IFN-β的产生和抗病毒先天免疫反应。我们得出的结论是,FAF1通过抑制活性磷酸化IRF3从细胞质到细胞核的转运,在负调控病毒诱导的IFN-β产生和抗病毒反应中发挥了新的作用。

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