NLRP11 attenuates Toll-like receptor signalling by targeting TRAF6 for degradation via the ubiquitin ligase RNF19A. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Wu, Chenglei; Su, Zexiong; Lin, Meng; Ou, Jiayu; Zhao, Wei; Cui, Jun; Wang, Rong-Fu
• Is Part Of: Nature communications. Volume 8:Issue 1(2017)
• Page Start: 1
• Page End: 15
• Publication Date: 2017-12
• Subjects: Biology -- Periodicals; Physical sciences -- Periodicals; 505
• DOI: 10.1038/s41467-017-02073-3
• Languages: English
• ISSNs: 2041-1723

Abstract

Abstract 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. NLRP11 is a primate-specific NOD-like receptor with unclear function. Here the authors show NLRP11 is an inhibitory protein that targets TRAF6 for K48 ubiquitination-mediated proteasomal degradation to limit inflammatory responses.