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2019年度論文動態

E3 ubiquitin ligase RNF170 inhibits innate immune responses by targeting and degrading TLR3 in murine cells.

Song X1, Liu S1, Wang W1, Ma Z1, Cao X1,2,3, Jiang M4

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Cell Mol Immunol. 2019 May 10

PMID: 31076723

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Abstract

Upon recognition of dsRNA, toll-like receptor 3 (TLR3) recruits the adaptor protein TRIF to activate IRF3 and NF-κB signaling, initiating innate immune responses. The ubiquitination of TLR3 downstream signaling molecules and their roles in the innate response have been discovered; however, whether TLR3 itself is ubiquitinated and then functionally involved remains to be elucidated. By immunoprecipitating TLR3-binding proteins in macrophages, we identified ring finger protein 170 (RNF170) as a TLR3-binding E3 ligase. RNF170 mediated the K48-linked polyubiquitination of K766 in the TIR domain of TLR3 and promoted the degradation of TLR3 through the proteasome pathway. The genetic ablation of RNF170 selectively augmented TLR3-triggered innate immune responses both in vitro and in vivo. Our results reveal a novel role for RNF170 in selectively inhibiting TLR3-triggered innate immune responses by promoting TLR3 degradation.