Negative Regulation of TLR Inflammatory Signaling by the SUMO-deconjugating Enzyme SENP6

	Negative Regulation of TLR Inflammatory Signaling by the SUMO-deconjugating Enzyme SENP6
	Liu, X; Chen, W; Wang, Q; Li, L; Wang, C
刊名	PLOS PATHOGENS
	2013
卷号	9 期号:6 页码:e1003480-e1003480
通讯作者	Liu, X (reprint author), Chinese Acad Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai Inst Biol Sci, Shanghai, Peoples R China.,cwang01@sibcb.ac.cn
英文摘要	The signaling of Toll-like receptors (TLRs) induces host defense against microbial invasion. Protein posttranslational modifications dynamically shape the strength and duration of the signaling pathways. It is intriguing to explore whether de-SUMOylation could modulate the TLR signaling. Here we identified SUMO-specific protease 6 (SENP6) as an intrinsic attenuator of the TLR-triggered inflammation. Depletion of SENP6 significantly potentiated the NF-kappa B-mediated induction of the proinflammatory genes. Consistently, SENP6-knockdown mice were more susceptible to endotoxin-induced sepsis. Mechanistically, the small ubiquitin-like modifier 2/3 (SUMO-2/3) is conjugated onto the Lysine residue 277 of NF-kappa B essential modifier (NEMO/IKK gamma), and this impairs the deubiquitinase CYLD to bind NEMO, thus strengthening the inhibitor of kappa B kinase (IKK) activation. SENP6 reverses this process by catalyzing the de-SUMOylation of NEMO. Our study highlights the essential function of the SENP family in dampening TLR signaling and inflammation.
学科主题	Microbiology; Parasitology; Virology
类目[WOS]	Microbiology ; Parasitology ; Virology
关键词[WOS]	NF-KAPPA-B ; TOLL-LIKE RECEPTORS ; KINASE COMPLEX ; GENOTOXIC STRESS ; IMMUNE-RESPONSE ; NEMO/IKK-GAMMA ; FEEDBACK LOOP ; IKK COMPLEX ; ACTIVATION ; UBIQUITINATION
收录类别	SCI
语种	英语
WOS记录号	WOS:000321206600064
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/394]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Liu, X,Chen, W,Wang, Q,et al. Negative Regulation of TLR Inflammatory Signaling by the SUMO-deconjugating Enzyme SENP6[J]. PLOS PATHOGENS,2013,9(6):e1003480-e1003480.
APA	Liu, X,Chen, W,Wang, Q,Li, L,&Wang, C.(2013).Negative Regulation of TLR Inflammatory Signaling by the SUMO-deconjugating Enzyme SENP6.PLOS PATHOGENS,9(6),e1003480-e1003480.
MLA	Liu, X,et al."Negative Regulation of TLR Inflammatory Signaling by the SUMO-deconjugating Enzyme SENP6".PLOS PATHOGENS 9.6(2013):e1003480-e1003480.