| First Author | Xiong MG | Year | 2020 |
| Journal | EMBO Rep | Volume | 21 |
| Issue | 3 | Pages | e48860 |
| PubMed ID | 31930677 | Mgi Jnum | J:285783 |
| Mgi Id | MGI:6394220 | Doi | 10.15252/embr.201948860 |
| Citation | Xiong MG, et al. (2020) RNF152 positively regulates TLR/IL-1R signaling by enhancing MyD88 oligomerization. EMBO Rep 21(3):e48860 |
| abstractText | Toll-like receptors (TLRs) are important pattern recognition receptors (PRRs) that are critical for the defense against invading pathogens. IL-1beta is an important pro-inflammatory cytokine that also plays pivotal roles in shaping the adaptive immune response. TLRs and interleukin-1 receptor (IL-1R) share similar cytosolic domains and signaling processes. In this study, we identify the E3 ubiquitin ligase RNF152 as a positive regulator of TLR/IL-1R-mediated signaling. Overexpression of RNF152 potentiates IL-1beta- and LPS-induced NF-kappaB activation in an ubiquitination-independent manner, whereas knockdown of RNF152 has the opposite effects. RNF152-deficient mice produce less inflammatory cytokines in response to LPS and are more resistant to LPS-induced lethal endotoxemia. Mechanistically, RNF152 interacts with the adaptor protein MyD88 and enhances oligomerization of MyD88, which is essential for the recruitment of downstream signaling components and activation of TLR/IL-1R-mediated signal transduction. Our findings suggest that RNF152-mediated oligomerization of MyD88 is important for TLR/IL-1R-mediated inflammatory response. |
