The Type I Interferon-IRF7 Axis Mediates Transcriptional Expression of Usp25 Gene
The Type I Interferon-IRF7 Axis Mediates Transcriptional Expression of Usp25 Gene
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I型干扰素-IRF7轴介导Usp25基因的转录表达
DOI：
10.1074/jbc.m116.718080
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发表时间：
2016-06-17
影响因子：
4.8
通讯作者：
Zhong, Bo
中科院分区：
文献类型：
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作者：
Ren, Yujie;Zhao, Yin;Zhong, Bo
病毒感染或脂多糖（LPS）处理诱导大量基因的表达，其产物在宿主抗病原体免疫和炎症中起关键作用。我们以前报道过，病毒感染或LPS处理后，泛素特异性蛋白酶25（USP 25）的表达显著上调，这是先天免疫信号传导所必需的。然而，这一现象背后的机制尚不清楚。在这项研究中，我们发现病毒感染诱导的Usp25上调在缺乏干扰素调节因子7（IRF7）或干扰素α受体1（IFNAR1）的细胞中减少，但不包括p65。仙台病毒或I型干扰素诱导的Usp25上调需要IRF7的从头蛋白合成。此外，IRF7直接结合到USP25启动子上的两个保守的IRF结合位点以驱动Usp25的转录，并且这两个位点的突变消除了仙台病毒诱导的IRF7介导的USP25启动子的激活。我们的研究揭示了一种以前未知的机制，病毒感染或LPS诱导USP25上调。
Viral infection or lipopolysaccharide (LPS) treatment induces expression of a large array of genes, the products of which play a critical role in host antipathogen immunity and inflammation. We have previously reported that the expression of ubiquitin-specific protease 25 (USP25) is significantly up-regulated after viral infection or LPS treatment, and this is essential for innate immune signaling. However, the mechanism behind this phenomenon is unclear. In this study, we found that viral infection-induced up-regulation of Usp25 is diminished in cells lacking interferon regulatory factor 7 (IRF7) or interferon alpha receptor 1 (IFNAR1) but not p65. Sendai virus- or type I interferon-induced up-regulation of Usp25 requires de novo protein synthesis of IRF7. Furthermore, IRF7 directly binds to the two conserved IRF binding sites on the USP25 promoter to drive transcription of Usp25, and mutation of these two sites abolished Sendai virus-induced IRF7-mediated activation of the USP25 promoter. Our study has uncovered a previously unknown mechanism by which viral infection or LPS induces up-regulation of USP25.