TNIP1和自受体调节了STING信号传递
Eric N Bunker1, Tara D Fischer1, Peng-Peng Zhu1
1Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health; Bethesda, MD, USA.
bioRxiv : the preprint server for biology
|June 26, 2025
概括
自受体和TNIP1与STING相关的囊泡结合,调节先天免疫力. 在TNIP1的负控制中,STING介导的NF-κB和干扰素信号传递独立于自.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 该cGAS-STING通路触发天生的免疫反应,涉及LC3B脂化和Golgi相关囊泡上的无处不在.
- 尽管与NF-κB信号相关联,但Golgi局部化聚比基链调节在免疫信号传递中的机制仍然不清楚.
研究的目的:
- 为了研究乌比奎和LC3B结合蛋白在STING介导的免疫信号传递中的作用.
- 阐明这些蛋白质调节STING相关囊泡和下游信号通路的机制.
主要方法:
- 研究了TNIP1和自受体 (p62,NBR1,NDP52,TAX1BP1,OPTN) 与STING诱导的囊泡的关联.
- 评估了TBK1激酶活性在囊泡招募和封存中的作用.
- 确定特定蛋白质域 (无素结合域,LC3B相互作用区域) 在招募中的重要性.
- 评估了TNIP1和OPTN对STING介导的NF-κB和干扰素信号传递的功能影响.
主要成果:
- TNIP1和自受体与STING诱导的Ub/LC3B标记的囊泡相关.
- p62和NBR1在周核区域中冗余地聚集这些囊泡.
- 对于TNIP1/受体的招募,不需要TBK1激酶活性,但有助于囊泡封存.
- TNIP1和OPTN的泛素结合域对于招募至关重要;OPTN也使用了TBK1依赖机制.
- TNIP1作为STING介导的NF-κB和干扰素信号的负调节剂.
结论:
- 自受体和TNIP1通过自独立的机制参与STING介导的免疫信号传递.
- TNIP1在负面调节由STING诱导的NF-κB和干扰素反应方面发挥着重要作用.
- 这些发现揭示了自相关蛋白在调节STING免疫力方面的新角色.
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