自噬蛋白(ATG13)激活IFNα表达的机制研究  

The Study on the Mechanism of IFNα Expression Stimulation by ATG13

作　　者：杨光美 韦泽艳 林馨 李良玉 王燮同 刘俊林[1] 赵永清[1] 马晓霞[1,2] YANG Guangmei;WEI Zeyan;LINXin;LI Liangyu;WANG Xietong;LIUJunlin;ZHAO Yongqing;MA Xiaoxia(College of Life Science and Engineering,Northwest Minzu University,Lanzhou 730010,China;Biomedical Research Center,Northwest Minzu University,Lanzhou 730030,China)

机构地区：[1]西北民族大学生命科学与工程学院,甘肃兰州730010 [2]西北民族大学生物医学研究中心,甘肃兰州730030

出　　处：《特产研究》2024年第4期54-62,71,共10页Special Wild Economic Animal and Plant Research

基　　金：中央高校基本科研业务费项目(31920220134)。

摘　　要：自噬相关蛋白基因13(Autophagy-related gene 13,atg13)在细胞自噬的发生过程中发挥着关键作用。然而,其在激活干扰素α(Interferon-α,IFN-α)的过程中所发挥的作用尚未阐明。基于对atg13基因的物种特异性的遗传特征,本研究选取人源atg13基因及人源胚胎肾细胞系(human embryonic kidney cell line,HEK 293T),作为研究atg13基因过表达与目标细胞中激活IFN-α信号通路的试验平台。结果表明atg13基因在刺激IFN-α产生的能力方面明显强于其激活IFN-β的活性。虽然atg13基因与IFN信号通路中的不同信号分子(MyD88,IKKα,TRAF6和IRF7)在转录及翻译水平上均有不同程度的相关性,但atg13基因过表达从而激活IRF7的磷酸化是IFN-α产生的关键因素。此外,ATG13蛋白与干扰素刺激应答原件(Interferon-stimulated response element,ISRE)的强烈互作也是atg13基因过表达激活IFN-α产生的重要环节。Autophagy-related gene 13(atg13)plays a pivotal role in autophagicmachinery.However,there is a big unexplored field involved in regulating interferon-α(IFN-α)production.Based on the species-specific lineages for genetic divergence of atg13 genes originated from different organisms,we used atg13 gene originated from Homo sapiens and human embryonic kidney(HEK 293T)cells to investigate the effects of atg13 overexpression on IFN-α signaling pathway.The showed results that atg13 overexpression has stronger induction of IFNthan that of IFN-β.Even though atg13 overexpression appears to interact with several important IFN-α signaling molecules(MyD88,IKKα,TRAF6 and IRF7)that the corresponding molecules display small changes at the transcriptional and translational levels to different degrees,ATG13 protein has a strong relationship with IRF7 phosphorylation involved in induction of IFN-α.In addition,there is an interesting phenomenon that ATG13 protein is able to trigger activities of interferon-stimulated response element(ISRE).Altogether,ATG13 protein has non-autophagic roles in triggering IRF7 phosphorylation and interacting with ISRE to directly initiate IFN-α production.

关 键 词：自噬相关蛋白基因13 干扰素Α 信号通路 磷酸化 干扰素刺激应答原件 

分 类 号：Q25[生物学—细胞生物学]