Essential and non-redundant roses of p48 (ISGF3 gamma) and IRF-1 in both type I and type II interferon responses, as revealed by gene targeting studies
Essential and non-redundant roses of p48 (ISGF3 gamma) and IRF-1 in both type I and type II interferon responses, as revealed by gene targeting studies
复制标题
DOI：
10.1046/j.1365-2443.1996.08008.x
复制
发表时间：
1996-01-01
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：
Kimura, T;Kadokawa, Y;Taniguchi, T
背景：干扰素（IFN）是一类细胞因子，赋予细胞对病毒感染的抵抗力。 I 型（IFN-α 和 β）和 II 型（IFN-γ）干扰素利用不同的受体，刺激这些受体会诱导下游靶基因的诱导。这些靶基因通常在其启动子区域内包含一个 IFN 响应元件，称为 ISRE（IFN 刺激响应元件），它结合异源三聚体转录因子 ISGF3（IFN 刺激基因因子 3），由 p48（ISGF3 γ）、Stat1（信号转导器和转录激活剂 1；α 或 β）和 Stat2 组成。 ISRE 序列与 IRF-E 序列重叠，IRF-E 结合另一种 IFN 诱导因子 IRF-1（IFN 调节因子-1）。 结果：我们通过基因打靶产生了缺乏 p48 的小鼠。我们证明 p48 在 I 型和 II 型 IFN 应答中都发挥着重要作用； LFN 诱导基因的激活以及 IFN-α 或 γ 建立的抗病毒状态均严重受损，并且在 p48 阴性胚胎成纤维细胞 (EF) 中不存在由两种 IFN 诱导的 ISRE 结合活性。此外，我们生成了 p48 和 IRF-1 均缺陷的小鼠，并发现至少一个 IFN 诱导基因依赖于这两种因子。 结论：p48 和 LRF-1 在细胞中并不发挥多余的功能，而是在 I 型和 II 型 IFN 反应中相互补充。
Background: Interferons (IFNs) are a class of cytokines which confer cellular resistance against viral infections. Type I (IFN-alpha and -beta) and type II (IFN-gamma) IFNs utilize distinct receptors, the stimulation of which results in the induction of downstream target genes. These target genes usually contain within their promoter region an IFN responsive element, termed ISRE (IFN stimulated response element) which binds a heterotrimeric transcription factor, ISGF3 (IFN-stimulated gene factor 3) consisting of p48 (ISGF3 gamma), Stat1 (Signal transducers and activators of transcription-1; alpha or beta), and Stat2. The ISRE sequence overlaps with that of IRF-E which binds another IFN-inducible factor, IRF-1 (IFN regulatory factor-1).Results: We generated mice lacking p48 by gene targeting. We show that p48 plays an essential role in both type I and type II IFN responses; activation of LFN-inducible genes and establishment of the antiviral state by IFN-alpha or -gamma are both severely impaired, and ISRE-binding activities induced by both IFNs are absent in the p48-negative embryonic fibroblasts (EFs). Furthermore, we generated mice deficient for both p48 and IRF-1 and found that at least one IFN-inducible gene is dependent on both factors.Conclusions: p48 and LRF-1 do not perform redundant functions in the cell, but rather complement one another in both type I and II IFN responses.