Regulation of IFN-alpha/beta genes: Evidence for a dual function of the transcription factor complex ISGF3 in the production and action of IFN-alpha/beta
Regulation of IFN-alpha/beta genes: Evidence for a dual function of the transcription factor complex ISGF3 in the production and action of IFN-alpha/beta
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DOI：
10.1046/j.1365-2443.1996.870287.x
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发表时间：
1996-11-01
期刊：
影响因子：
2.1
通讯作者：
Taniguchi, T
中科院分区：
文献类型：
--
作者：
Harada, H;Matsumoto, M;Taniguchi, T
背景：干扰素（IFN）在病毒感染细胞中的有效产生是宿主防御的一个重要方面。转录因子复合物ISGF 3（IFN-刺激基因因子3）最初被鉴定为IFN信号的关键介质;它在IFN受体（IFNR）刺激后形成，并结合ISRE（IFN-刺激反应元件）以激活IFN-诱导基因。它最近已被证明，ISGF 3，p48（ISGF 3 γ）的DNA结合成分也结合到病毒诱导的元素在IFN-α/β基因，表明一个潜在的新的作用p48在IFN production.Results：从小鼠的原代细胞与有针对性的破坏p48基因显示病毒诱导的IFN-α/β基因表达的严重缺陷。在缺乏I型IFNR或Stat 1的细胞中也观察到类似的缺陷，进一步证明了IFN信号在这些IFN基因诱导中的作用。ISGF 3实际上结合IFN-α/β启动子内的病毒诱导元件。我们还提供的证据表明，这些元素是另外控制的一个身份不明的因素（S），这大概触发IFN基因induction.Conclusions的初级阶段：我们的研究结果表明，IFN信号转导复合物ISGF 3在IFN生产中起着至关重要的作用，并建议ISGF 3可能直接参与IFN-α/β启动子的激活。ISGF 3的这种双重功能可以确保该细胞因子系统在宿主防御中的有效操作。
Background: Efficient production of interferons (IFNs) in virally infected cells is an essential aspect of the host defence. The transcription factor complex ISGF3 (IFN-stimulated gene factor 3) was originally identified as a critical mediator of the IFN signal; it is formed upon IFN receptor (IFNR) stimulation and binds to ISREs (IFN-stimulated response elements) to activate IFN-inducible genes. It has recently been shown that the DNA binding component of ISGF3, p48 (ISGF3 gamma) also binds to virus-inducible elements in the IFN-alpha/beta genes, suggesting a potential new role of p48 in IFN production.Results: Primary cells from mice with a targeted disruption of the p48 gene show severe defects in virus-induced IFN-alpha/beta gene expression. A similar defect was also observed in cells lacking type I IFNR or Stat1, further demonstrating the role of IFN signalling in the induction of these IFN genes. ISGF3 in fact binds to the virus-inducible elements within the IFN-alpha/beta promoters. We also provide evidence showing that these elements are additionally controlled by an unidentified factor(s) which presumably triggers the primary phase of IFN gene induction.Conclusions: Our results demonstrate that the IFN signal transducing complex ISGF3 plays a crucial role in IFN production and suggest that ISGF3 may participate directly in the activation of IFN-alpha/beta promoters. This dual function of ISGF3 may insure the efficient operation of this cytokine system in the host defence.