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RNF152 positively regulates TLR/IL-1R signaling by enhancing MyD88 oligomerization.
EMBO Reports ( IF 6.5 ) Pub Date : 2020-01-13 , DOI: 10.15252/embr.201948860
Mei-Guang Xiong 1, 2 , Zhi-Sheng Xu 1 , Yu-Hui Li 1, 2 , Su-Yun Wang 1 , Yan-Yi Wang 1 , Yong Ran 1
Affiliation  

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.

中文翻译:

RNF152 通过增强 MyD88 寡聚化正向调节 TLR/IL-1R 信号传导。

Toll 样受体 (TLR) 是重要的模式识别受体 (PRR),对于防御入侵病原体至关重要。IL-1β 是一种重要的促炎细胞因子,在塑造适应性免疫反应中也起着关键作用。TLR 和白细胞介素 1 受体 (IL-1R) 具有相似的胞质结构域和信号传导过程。在这项研究中,我们将 E3 泛素连接酶 RNF152 鉴定为 TLR/IL-1R 介导的信号传导的正调节剂。RNF152 的过表达以不依赖泛素化的方式增强 IL-1β 和 LPS 诱导的 NF-κB 活化,而 RNF152 的敲低具有相反的效果。RNF152 缺陷小鼠对 LPS 的反应产生较少的炎性细胞因子,并且对 LPS 诱导的致死性内毒素血症更具抵抗力。机械地,RNF152 与衔接蛋白 MyD88 相互作用并增强 MyD88 的寡聚化,这对于募集下游信号成分和激活 TLR/IL-1R 介导的信号转导至关重要。我们的研究结果表明,RNF152 介导的 MyD88 寡聚化对 TLR/IL-1R 介导的炎症反应很重要。
更新日期:2020-03-04
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