| First Author | Song X | Year | 2020 |
| Journal | Cell Mol Immunol | Volume | 17 |
| Issue | 8 | Pages | 865-874 |
| PubMed ID | 31076723 | Mgi Jnum | J:315640 |
| Mgi Id | MGI:6829458 | Doi | 10.1038/s41423-019-0236-y |
| Citation | Song X, et al. (2020) E3 ubiquitin ligase RNF170 inhibits innate immune responses by targeting and degrading TLR3 in murine cells. Cell Mol Immunol 17(8):865-874 |
| abstractText | Upon recognition of dsRNA, toll-like receptor 3 (TLR3) recruits the adaptor protein TRIF to activate IRF3 and NF-kappaB 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. |
