STING诱导M1无素链的HOIP介导合成,以刺激NF-κB信号传递
Tara D Fischer1, Eric N Bunker2, Peng-Peng Zhu2
1Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. fischertad@nih.gov.
The EMBO journal
|November 23, 2024
概括
STING激活通过NF-κB和IRF3通路诱导先天性免疫信号传递. 卢巴克酶HOIP合成了与M1结合的泛素链,这对于这种依赖于STING的免疫反应至关重要.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 由循环二核酸激活的STING (干扰素基因刺激器) 激活会触发IRF3和NF-κB信号,并与LC3B脂化一起进行.
- 由STING介导的NF-κB激活背后的机制尚未完全阐明.
研究的目的:
- 研究乌比奎丁链和LUBAC在STING诱导的NF-κB和IRF3信号传递中的作用.
- 为了澄清STING激活,LC3B脂化和免疫基因表达之间的关系.
主要方法:
- 利用了人类的THP1单细胞和来自小鼠骨髓的巨细胞.
- 评估了STING激活,M1-ubiquitin链形成,HOIP招募以及NF-κB/IRF3信号传递.
- 研究了HOIP缺陷对STING诱导反应的影响.
主要成果:
- STING的激活促进了M1-ubiquitin链的形成和HOIP的招募到LC3B相关的戈尔吉膜.
- 缺少HOIP会取消M1-ubiquitin链的形成,并损害STING诱导的NF-κB和IRF3信号传递.
- 在M1-ubiquitin链合成或免疫基因表达中,STING诱导的LC3B脂化并不必不可少.
结论:
- 通过LUBAC介导的M1连接的泛素链的合成是STING诱导的先天性免疫信号传递的关键机制.
- 在依赖于STING的NF-κB和IRF3激活中,HOIP起着至关重要的作用.
- 这些发现阐明了一种通过STING来激活先天性免疫系统的新途径.
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