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RNF 152 positively regulates TLR / IL ‐1R signaling by enhancing MyD88 oligomerization
Author(s) -
Xiong MeiGuang,
Xu ZhiSheng,
Li YuHui,
Wang SuYun,
Wang YanYi,
Ran Yong
Publication year - 2020
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201948860
Subject(s) - microbiology and biotechnology , signal transduction , chemistry , biology
Abstract Toll‐like receptors ( TLR s) are important pattern recognition receptors ( PRR s) that are critical for the defense against invading pathogens. IL ‐1β is an important pro‐inflammatory cytokine that also plays pivotal roles in shaping the adaptive immune response. TLR s and interleukin‐1 receptor ( IL ‐1R) share similar cytosolic domains and signaling processes. In this study, we identify the E3 ubiquitin ligase RNF 152 as a positive regulator of TLR / IL ‐1R‐mediated signaling. Overexpression of RNF 152 potentiates IL ‐1β‐ and LPS ‐induced NF ‐κB activation in an ubiquitination‐independent manner, whereas knockdown of RNF 152 has the opposite effects. RNF 152‐deficient mice produce less inflammatory cytokines in response to LPS and are more resistant to LPS ‐induced lethal endotoxemia. Mechanistically, RNF 152 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 RNF 152‐mediated oligomerization of MyD88 is important for TLR / IL ‐1R‐mediated inflammatory response.