ARRDC4 regulates enterovirus 71-induced innate immune response by promoting K63 polyubiquitination of MDA5 through TRIM65.

	ARRDC4 regulates enterovirus 71-induced innate immune response by promoting K63 polyubiquitination of MDA5 through TRIM65.
	Meng, Jun; Yao, Zhenyu; He, Yaqing; Zhang, Renli; Zhang, Yanwei; Yao, Xiangjie; Yang, Hong; Chen, Long; Zhang, Zhen; Zhang, Hailong
刊名	CELL DEATH & DISEASE
	2017
文献子类	期刊论文
英文摘要	Enterovirus 71 (EV71) is the main causative agent of hand, foot and mouth disease (HFMD), which induces significantly elevated levels of cytokines and chemokines, leading to local or system inflammation and severe complications, whereas the underlying regulatory mechanisms and the inflammatory pathogenesis remain elusive. ARRDC4 is one member of arrestins family, having important roles in glucose metabolism and G-protein-coupled receptors (GPCRs) related physiological and pathological processes, however, the function of ARRDC4 in innate immune system is largely unknown. Here we identified that ARRDC4 expression was increased after EV71 infection in THP-1-derived macrophages and verified in EV71-infected HFMD patients and the healthy candidates. The expression level of ARRDC4 was positively correlated with the serum concentration of IL-6, TNF-a and CCL3 in clinical specimens. ARRDC4interacted with MDA5 via the arrestin-like N domain, and further recruited TRIM65 to enhance the K63 ubiquitination of MDA5, resulting in activation of the downstream innate signaling pathway and transcription of proinflammatory cytokines during EV71 infection. Our data highlight new function of ARRDC4 ininnate immunity, contributing to the better understanding about regulation of MDA5 activation after EV71 infection, and also suggest ARRDC4 may serve as a potential target for intervention of EV71-induced inflammatory response.
URL标识	查看原文
语种	英语
内容类型	期刊论文
源URL	[http://ir.siat.ac.cn:8080/handle/172644/12143]
专题	深圳先进技术研究院_医工所
作者单位	CELL DEATH & DISEASE
推荐引用方式 GB/T 7714	Meng, Jun,Yao, Zhenyu,He, Yaqing,et al. ARRDC4 regulates enterovirus 71-induced innate immune response by promoting K63 polyubiquitination of MDA5 through TRIM65.[J]. CELL DEATH & DISEASE,2017.
APA	Meng, Jun.,Yao, Zhenyu.,He, Yaqing.,Zhang, Renli.,Zhang, Yanwei.,...&Cheng, Jinquan.(2017).ARRDC4 regulates enterovirus 71-induced innate immune response by promoting K63 polyubiquitination of MDA5 through TRIM65..CELL DEATH & DISEASE.
MLA	Meng, Jun,et al."ARRDC4 regulates enterovirus 71-induced innate immune response by promoting K63 polyubiquitination of MDA5 through TRIM65.".CELL DEATH & DISEASE (2017).