Journal
EMBO REPORTS
Volume 21, Issue 3, Pages -Publisher
WILEY
DOI: 10.15252/embr.201948860
Keywords
IL-1 beta; LPS; MyD88; RNF152; toll-like receptor
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Funding
- Chinese Academy of Sciences [XDB29010302]
- Youth Innovation Promotion Association CAS [2017382]
- National Natural Science Foundation of China [31621061]
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Toll-like receptors (TLRs) are important pattern recognition receptors (PRRs) that are critical for the defense against invading pathogens. IL-1 beta 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-1 beta- and LPS-induced NF-kappa B 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.
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