RNF 152 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, 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.

A conserved ubiquitin- and ESCRT-dependent pathway to regulate human lysosomal membrane proteins

“…Of note, a small fraction of GFP-RNF152 puncta do not colocalize with LAMP2 (white arrows in Figure 1C). This observation is consistent with a recent study indicating that RNF152 could also localize to endosomes (Xiong et al, 2020).…”

“…Because a fraction of RNF152 localizes to the endosome (white arrows in Figure 1C, Xiong et al, 2020), it is possible that the observed degradation is due to the endosomal degradation of RNF152. To ensure that the lysosome population of RNF152 is fast-degrading, we performed the Lyso-IP experiment using cells collected before and after 2 hours of CHX treatment.…”

Genome-wide scan for selection signatures reveals novel insights into the adaptive capacity in local North African cattle

“…For instance, the outlier window on BTA01 (at position: 17,740,000-19,640,000 bp), contained 6 protein coding genes including TMPRSS15 and CHODL, two genes that were reported to be under selection in the Iraqi indigenous cattle 13 . Similarly, the candidate region on the BTA24 (at position: 59,660,000-61,790,000 bp), harboured RNF152 gene which positively regulates Toll-like receptors (TLRs) which are important pattern recognition receptors that are critical for the defence against invading pathogens 36 . RNF152 gene was reported to be involved in local adaptations in the Ainu, a hunter-gatherer population of northern Japan 37 .…”

TcpC inhibits toll-like receptor signaling pathway by serving as an E3 ubiquitin ligase that promotes degradation of myeloid differentiation factor 88

“…The innate immune system senses invading pathogens by pattern recognition receptors that include the NOD-like receptors, RIG-like receptors, cytosolic DNA receptors, and TLRs [ 38 ]. TLRs recognize various microbial components, such as proteins, lipids, lipoproteins, nucleic acids, glycoproteins, leading to the activation of innate immune cells [ 39 ].…”