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通过核因子κB途径对炎症反应的泛素化调节

Ubiquitination regulation of inflammatory responses through NF-κB pathway.

作者信息

Wu Yunbing, Kang Jingjing, Zhang Lu, Liang Zhaofeng, Tang Xudong, Yan Yongmin, Qian Hui, Zhang Xu, Xu Wenrong, Mao Fei

机构信息

Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu UniversityZhenjiang 212013, Jiangsu, China.

Jiangsu University of Science and TechnologyZhenjiang 212018, Jiangsu, China.

出版信息

Am J Transl Res. 2018 Mar 15;10(3):881-891. eCollection 2018.

Abstract

The development of inflammation is mutually affected with damaged DNA and the abnormal expression of protein modification. Ubiquitination, a way of protein modification, plays a key role in regulating various biological functions including inflammation responses. The ubiquitin enzymes and deubiquitinating enzymes (DUBs) jointly control the ubiquitination. The fact that various ubiquitin linkage chains control the fate of the substrate suggests that the regulatory mechanisms of ubiquitin enzymes are central for ubiquitination. In inflammation diseases, the pro-inflammatory transcription factor NF-κB regulates transcription of pro-labour mediators in response to inflammatory stimuli and expression of numerous genes that control inflammation which is associated with ubiquitination. The ubiquitination regulates NF-κB signaling pathway with many receptor families, including NOD-like receptors (NLR), Toll-like receptors (TLR) and RIG-I-like receptors (RLR), mainly by K63-linked polyubiquitin chains. In this review, we highlight the study of ubiquitination in the inflammatory signaling pathway including NF-κB signaling regulated by ubiquitin enzymes and DUBs. Furthermore, it is emphasized that the interaction of ubiquitin-mediated inflammatory signaling system accurately regulates the inflammatory responses.

摘要

炎症的发展与受损的DNA以及蛋白质修饰的异常表达相互影响。泛素化作为一种蛋白质修饰方式,在调节包括炎症反应在内的各种生物学功能中起着关键作用。泛素酶和去泛素化酶(DUBs)共同控制泛素化过程。各种泛素连接链控制底物命运这一事实表明,泛素酶的调节机制是泛素化的核心。在炎症性疾病中,促炎转录因子NF-κB响应炎症刺激调节促炎介质的转录以及众多控制炎症的基因的表达,这与泛素化相关。泛素化主要通过K63连接的多聚泛素链,利用包括NOD样受体(NLR)、Toll样受体(TLR)和RIG-I样受体(RLR)在内的许多受体家族调节NF-κB信号通路。在本综述中,我们重点介绍了炎症信号通路中泛素化的研究,包括泛素酶和DUBs调节的NF-κB信号通路。此外,强调了泛素介导的炎症信号系统的相互作用精确调节炎症反应。

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