青鱼IKKε激活STAT1的分子机制研究

JAK-STAT信号通路是宿主抗病毒先天免疫的重要组成；STAT1的磷酸化修饰对其活化和入核诱导干扰素刺激基因（ISG）的转录至关重要。哺乳类IKKε是STAT1磷酸化的重要激酶之一；目前尚无鱼类IKKε与STAT1关系的报道。本工作组前期鉴定了青鱼两个STAT1基因（STAT1a和STAT1b）的抗病毒活性，并发现青鱼IKKε促进STAT1b入核和提高其抗病毒能力。为了阐明青鱼IKKε激活STAT1的分子机制，本项目拟开展如下研究：1.研究青鱼IKKε与STAT1a/b的相互作用关系；2.研究青鱼IKKε磷酸化STAT1a/b的机制；3. 研究IKKε磷酸化STAT1a/b与STAT1a/b抗病毒活性的关联。青鱼是我国重要经济养殖鱼类，其先天免疫机制缺乏系统和深入的研究。本项目希冀揭示青鱼IKKε磷酸化STAT1在宿主先天免疫激活中的功能机制，为系统阐明青鱼抗病毒先天免疫机制奠定基础。

JAK-STAT signaling pathway plays the key role in the antiviral innate immunity. The phosphorylation of STAT1 is essential for the activation and nuclear translocation of STAT1, which leads to the transcription of the interferon-stimulated gene (ISGs). Mammlian IKKε has been reported to be an important kinase for the phosphorylation of STAT1; however, there is no report on the relationship between IKKε and STAT1 in teleost. In our previous study, the antiviral activities of two STAT1 homologues (bcSTAT1a and bcSTAT1b) of black carp (Mylopharyngodon piceus) have been identified, in which black carp IKKε (bcIKKε) improved the nuclear transfer of bcSTAT1b and enhanced its antiviral activity. In order to elucidate the collaboration between bcIKKε and bcSTAT1, the following researches will be carried out in this study: 1. Investigating the interaction between bcIKKε and bcSTAT1a/b. 2. Investigating the mechanism behind the bcSTAT1 phosphorylation by bcIKKε. 3. Investigating the relationship between the phosphorylation of bcSTAT1a/b by bcIKKε and the antiviral activity of STAT1a/b. Black carp is an important fresh water species in China; however, the innate immune system of black carp needs to be extensive studied. This study is aimed to reveal the mechanism of bcSTAT1 phosphorylation by bcIKKε and to build a foundation for the elucidation of the antiviral innate immunity of black carp.