MARCH5通过抑制氧化STING的聚合物形成来促进STING通路的激活
Kyungpyo Son1, Seokhwan Jeong1, Eunchong Eom1
1Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
EMBO reports
|November 2, 2023
概括
线粒体结合酶MARCH5无处不在地化STING,增强免疫反应. 它的缺乏会导致氧化应激,形成不活跃的STING聚合物,但MARCH5的无化会阻止这种情况,平衡STING的激活.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 生物化学 生化学
背景情况:
- 干扰素基因刺激器 (STING) 对于天生的免疫DNA传感至关重要.
- 通过转化后修饰 (PTM) 和聚合物形成来调节STING活动.
- 不同的PTM和STING聚合物结构之间的相互作用仍然不太清楚.
研究的目的:
- 调查线粒体结合酶MARCH5在调节STING活动中的作用.
- 阐明MARCH5如何影响STING的翻译后修饰和聚合物形成.
- 为了了解MARCH5,氧化应激和STING激活之间的关系.
主要方法:
- 使用生物化学试验研究STING在MARCH5.5之前的无处不在性.
- 研究了MARCH5缺陷对STING聚合和氧化的影响.
- 分析了STING氨酸205氧化对聚合物形成的影响.
主要成果:
- 线粒体结合酶MARCH5使STING无处不在,增强其激活.
- 长期的MARCH5缺乏导致反应性氧物种的产生.
- 在MARCH5缺乏的细胞中,氧化应激通过氨酸205氧化促进了不活跃的STING聚合物形成.
- 通过MARCH5介导的全方位化抑制了氧化诱导的STING聚合物形成.
结论:
- MARCH5通过平衡无处不在和聚合物形成,在调节STING方面发挥了双重作用.
- 在氧化条件下,MARCH5活性对于防止不活性STING聚合物的形成至关重要.
- 通过MARCH5对STING激活的控制取决于细胞的氧化状态.
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