TY - JOUR
T1 - NLRP11 attenuates Toll-like receptor signalling by targeting TRAF6 for degradation via the ubiquitin ligase RNF19A
AU - Wu, Chenglei
AU - Su, Zexiong
AU - Lin, Meng
AU - Ou, Jiayu
AU - Zhao, Wei
AU - Cui, Jun
AU - Wang, Rong Fu
N1 - Funding Information:
This work was supported by the National Natural Science Foundation of China (31370869, 91629101, 31522018, and 81572766), the National Key Basic Research Program of China (2015CB859800, 2014CB910800, 2014CB745203, and 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 and 2016ZT06S029), the Science and Technology Planning Project of Guangdong Province (2015B020228002), and was in part supported by grants (CA101795) from NCI, NIH (to R.-F.W.).
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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-κB 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.
AB - 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-κB 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.
UR - http://www.scopus.com/inward/record.url?scp=85038120122&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85038120122&partnerID=8YFLogxK
U2 - 10.1038/s41467-017-02073-3
DO - 10.1038/s41467-017-02073-3
M3 - Article
C2 - 29215004
AN - SCOPUS:85038120122
SN - 2041-1723
VL - 8
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1977
ER -