The adaptor protein TRAF6 has a central function in Toll-like receptor (TLR) signalling, yet the molecular mechanisms controlling its activity and stability are unclear. Here we show that NLRP11, a primate specific gene, inhibits TLR signalling by targeting TRAF6 for degradation. NLRP11 recruits the ubiquitin ligase RNF19A to catalyze K48-linked ubiquitination of TRAF6 at multiple sites, thereby leading to the degradation of TRAF6. Furthermore, deficiency in either NLRP11 or RNF19A abrogates K48-linked ubiquitination and degradation of TRAF6, which promotes activation of NF-kappa B and MAPK signalling and increases the production of proinflammatory cytokines. Therefore, our findings identify NLRP11 as a conserved negative regulator of TLR signalling in primate cells and reveal a mechanism by which the NLRP11-RNF19A axis targets TRAF6 for degradation.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [31370869, 91629101, 31522018, 81572766]; National Key Basic Research Program of ChinaNational Basic Research Program of China [2015CB859800, 2014CB910800, 2014CB745203, 2017YFA0103802]; Shenzhen Peacock Plan [KQTD20130416114522736]; Shenzhen Technology Research Program [JSGG20160301161836370]; Guangdong Natural Science Funds for Distinguished Young Scholar [S2013050014772]; Guangdong Innovative Research Team Program [2011Y035, 2016ZT06S029]; Science and Technology Planning Project of Guangdong Province [2015B020228002]; NCI, NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [CA101795]
语种：
外文
被引次数：
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中科院(CAS)分区：
出版当年[2017]版：
大类|1 区综合性期刊
小类|1 区综合性期刊
最新[2023]版：
大类|1 区综合性期刊
小类|1 区综合性期刊
第一作者：
第一作者机构：[1]Sun Yat Sen Univ, Zhongshan Sch Med, Guangzhou 510080, Guangdong, Peoples R China;
通讯作者：
通讯机构：[2]Sun Yat Sen Univ, Sch Life Sci, Key Lab Gene Engn, State Key Lab Biocontrol,Minist Educ, Guangzhou 510006, Guangdong, Peoples R China;[3]Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, Guangzhou 510080, Guangdong, Peoples R China;[4]Houston Methodist Res Inst, Ctr Inflammat & Epigenet, Houston, TX 77030 USA;[5]Cornell Univ, Dept Microbiol & Immunol, Weill Cornell Med, New York, NY 10065 USA;[6]Texas A&M Univ, Inst Biosci & Technol, Coll Med, Houston, TX 77030 USA
推荐引用方式(GB/T 7714)：
Wu Chenglei,Su Zexiong,Lin Meng,et al.NLRP11 attenuates Toll-like receptor signalling by targeting TRAF6 for degradation via the ubiquitin ligase RNF19A[J].NATURE COMMUNICATIONS.2017,8:-.doi:10.1038/s41467-017-02073-3.
APA：
Wu, Chenglei,Su, Zexiong,Lin, Meng,Ou, Jiayu,Zhao, Wei...&Wang, Rong-Fu.(2017).NLRP11 attenuates Toll-like receptor signalling by targeting TRAF6 for degradation via the ubiquitin ligase RNF19A.NATURE COMMUNICATIONS,8,
MLA：
Wu, Chenglei,et al."NLRP11 attenuates Toll-like receptor signalling by targeting TRAF6 for degradation via the ubiquitin ligase RNF19A".NATURE COMMUNICATIONS 8.(2017):-
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