NLRP11 Attenuates Toll-like Receptor Signalling by Targeting TRAF6 for Degradation Via the Ubiquitin Ligase RNF19A

Overview

Journal Nat Commun

Specialty Biology

Date 2017 Dec 8

PMID 29215004

Citations 45

Authors

Chenglei Wu

Zexiong Su

Meng Lin

Jiayu Ou

Wei Zhao

Jun Cui

Rong-Fu Wang

Affiliations

Soon will be listed here.

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.

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