脂多糖信号通路中的蛋白质修饰

Post-translational Modifications in Regulation of Lipopolysaccharide-activated Signal Transduction Pathway

革兰氏阴性细菌外膜中的脂多糖,又称内毒素,感染宿主后可导致脓毒症、脓毒性休克和多器官功能障碍综合症.脂多糖借助信号转导通路诱发宿主的应答,刺激免疫细胞产生大量具有致热效应的炎性细胞因子,引起免疫系统的过度活化.近年来,研究脂多糖受体TLR4及其信号转导在先天免疫和获得性免疫中的作用,以及脂多糖信号通路的复杂调控机制取得了突破性进展.其中蛋白质翻译后修饰参与脂多糖信号通路调节的研究成为这一领域的新热点之一.本文总结了磷酸化修饰、泛素化修饰、ISG15化修饰和SUMO化修饰在调节脂多糖信号通路方面的作用.不仅对被修饰蛋白如何传递和调节脂多糖信号以及翻译后修饰在该过程中的作用进行了阐述,还着眼于不同翻译后修饰形式之间的关联.脂多糖信号通路的深入研究不但有助于阐明内毒素相关疾病的分子机理,还可为临床预防和治疗革兰氏阴性细菌感染所致疾病提供新靶点.

As an endotoxin of which major component is the outer leaflet of Gram negative bacteria,lipopolysaccharide（LPS） may cause sepsis,septic shock and multiple organ dysfunction syndrome.Host responses to LPS are caused by the over-activation of immune cells and the excessive secretion of inflammatory mediators,such as cytokines been induced downstream of the host signal transduction pathways.In recent years,rapid progresses in LPS related research has been achieved as a result of the discovery of the LPS receptor-TLR4 and its critical signaling roles in both innate and adaptive immunity,which allowed a better appreciation of the complexity of the LPS signal pathways.In this review,the post-translational modifications involved in LPS-activated signal transduction pathways will be summarized,including protein phosphorylation,ubiquitination,ISGylation and SUMOylation.In particular,we will focus on how these modified proteins conduct and regulate LPS signals,and how different post-translational modifications regulate the functions of a protein.Unraveling the fine-tuning of LPS signals will not only help to understand the molecular mechanism of endotoxin-related diseases,but also provide potential targets for the prevention and control of diseases caused Gram negative bacteria.