RNF152 positively regulates TLR/IL-1R signaling by enhancing MyD88 oligomerization.

ABSTRACT: Toll-like receptors (TLRs) are important pattern recognition receptors (PRRs) 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. 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-1β- and LPS-induced NF-κB 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, RNF15

SUBMITTER: Xiong MG 

PROVIDER: S-EPMC7054668 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature