ER-localized Hrd1 ubiquitinates and inactivates Usp15 to promote TLR4-induced inflammation during bacterial infection

doi:10.1038/s41564-019-0542-2

	ER-localized Hrd1 ubiquitinates and inactivates Usp15 to promote TLR4-induced inflammation during bacterial infection
	Lu, Yao 1; Qiu, Ying 1; Chen, Peng 2; Chang, Haishuang 3; Guo, Luqiang 3; Zhang, Fang 4,5; Ma, Li 1; Zhang, Chi 1; Zheng, Xin 1; Xiao, Jun 1; Zhong, Ruiyue 1; Han, Lei 1; Xu, Xiaoyan 1,6; Zhang, Yanbo 1,7; Li, Dangsheng 1; Zhong, Guisheng8 ; Boyton, Rosemary 9,10; Huang, Ying 3; He, Yongning 3; Hu, Ronggui 2; Wei, Bin 4,5,11; Wang, Hongyan 1,11
	2019-12
发表期刊	NATURE MICROBIOLOGY
ISSN	2058-5276
卷号	4 期号:12 页码:2331-2346
发表状态	已发表
DOI	10.1038/s41564-019-0542-2
摘要	The special organelle-located MAVS, STING and TLR3 are important for clearing viral infections. Although TLR4 triggers NF-kappa B activation to produce pro-inflammatory cytokines for bacterial clearance, effectors with special organelle localization have not been identified. Here, we screened more than 280 E3 ubiquitin ligases and discovered that the endoplasmic reticulum-located Hrd1 regulates TLR4-induced inflammation during bacterial infection. Hrd1 interacts directly with the deubiquitinating enzyme Usp15. Unlike the classical function of Hrd1 in endoplasmic reticulum-associated degradation, Usp15 is not degraded but loses its deubiquitinating activity for I kappa B alpha deubiquitination, resulting in excessive NF-kappa B activation. Importantly, Hrd1 deficiency in macrophages protects mice against lipopolysaccharide-induced septic shock, and knockdown of Usp15 in Hrd1-knockout macrophages restores the reduced IL-6 production. This study proposes that there is crosstalk between Hrd1 and TLR4, thereby linking the endoplasmic reticulum-plasma membrane function during bacterial infection.
收录类别	SCI ; SCIE
语种	英语
资助项目	State Key Laboratory of Cell Biology, SIBCB, CAS[SKL CBKF2013003]
WOS研究方向	Microbiology
WOS类目	Microbiology
WOS记录号	WOS:000499071100035
出版者	NATURE PUBLISHING GROUP
WOS关键词	NF-KAPPA-B ; RETICULUM-ASSOCIATED DEGRADATION ; PROTEIN ; LIGASE ; ACTIVATION ; ADAPTER ; APOPTOSIS ; STRESS ; VIRUS ; RNA
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/104496
专题	iHuman研究所_PI研究组_钟桂生组生命科学与技术学院
通讯作者	Hu, Ronggui; Wei, Bin; Wang, Hongyan
作者单位	1.Chinese Acad Sci, Univ Chinese Acad Sci, Key Lab Syst Biol,State Key Lab Cell Biol,CAS Ctr, Shanghai Inst Biochem & Cell Biol,Innovat Ctr Cel, Shanghai, Peoples R China 2.Chinese Acad Sci, Univ Chinese Acad Sci, State Key Lab Mol Biol,CAS Ctr Excellence Mol Cel, Key Lab Syst Biol,Shanghai Inst Biochem & Cell Bi, Shanghai, Peoples R China 3.Chinese Acad Sci, Univ Chinese Acad Sci,Shanghai Inst Biochem & Cel, Natl Ctr Prot Sci Shanghai,CAS Ctr Excellence Mol, State Key Lab Mol Biol,Shanghai Sci Res Ctr,Shang, Shanghai, Peoples R China 4.Chinese Acad Sci, Wuhan Inst Virol, Wuhan, Hubei, Peoples R China 5.Shanghai Univ, Sch Life Sci, Shanghai, Peoples R China 6.NCI, Expt Immunol Branch, US Natl Inst Hlth, Bethesda, MA USA 7.Harvard Med Sch, Dept Microbiol & Immunobiol, Div Immunol, Boston, MA 02115 USA 8.ShanghaiTech Univ, Sch Life Sci & Technol, iHuman Inst, Shanghai, Peoples R China 9.Imperial Coll London, Fac Med, Dept Infect Dis, Lung Immunol Grp,Adult Infect Dis, London, England 10.Royal Brompton & Harefield NHS Fdn Trust, Dept Resp Med, London, England 11.Tongji Univ, Shanghai Peoples Hosp 10, Canc Ctr, Sch Med, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Lu, Yao,Qiu, Ying,Chen, Peng,et al. ER-localized Hrd1 ubiquitinates and inactivates Usp15 to promote TLR4-induced inflammation during bacterial infection[J]. NATURE MICROBIOLOGY,2019,4(12):2331-2346.
APA	Lu, Yao.,Qiu, Ying.,Chen, Peng.,Chang, Haishuang.,Guo, Luqiang.,...&Wang, Hongyan.(2019).ER-localized Hrd1 ubiquitinates and inactivates Usp15 to promote TLR4-induced inflammation during bacterial infection.NATURE MICROBIOLOGY,4(12),2331-2346.
MLA	Lu, Yao,et al."ER-localized Hrd1 ubiquitinates and inactivates Usp15 to promote TLR4-induced inflammation during bacterial infection".NATURE MICROBIOLOGY 4.12(2019):2331-2346.