由 HERCs 进行的 ISGylation 促进了 STING 激活
Ying Qin1, Min Wang2, Xintong Meng1
1Key Laboratory for Experimental Teratology of the Chinese Ministry of Education and Key Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Cell reports
|April 23, 2024
概括
含有 HECT 域和 RCC1 类域的蛋白质 (HERCs) 调节干扰素基因 (STING) 蛋白质的刺激器.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 病毒学 病毒学
背景情况:
- 干扰素基因刺激器 (STING) 蛋白激活对于对病原体的天生的免疫力至关重要.
- 包括ISGylation在内的翻译后修饰调节STING活动,但它们的具体作用仍然不完全理解.
- 了解STING调节是开发宿主导的抗病毒疗法的关键.
研究的目的:
- 阐明ISG15修饰 (ISGylation) 在控制STING稳定性和激活中的作用.
- 研究HECT域和RCC1-类域含蛋白 (HERCs) 在STING介导的免疫反应中的功能.
- 在STING调控中探索ISGylation和ubiquitination之间的相互作用.
主要方法:
- 研究了在 HERC 蛋白质存在或不存在的情况下的 STING 蛋白质稳定性和激活.
- 使用了简单疹病毒1感染的体外和体内模型.
- 分析了严重急性呼吸系统综合征冠状病毒2 papain-like 蛋白酶对STING ISGylation的影响.
主要成果:
- HERC 蛋白 (HERC5/HERC6) 在 K150 中调解 STING 的 ISGylation,防止其无处不在和降解.
- 赫尔克6缺乏会损害I型干扰素的反应,并在感染简单疹病毒1期间增强病毒复制.
- SARS-CoV-2 帕帕因类蛋白酶通过裂解 HERC5 介导的 STING ISGylation 来对抗宿主防御.
结论:
- HERC介导的ISGylation是控制STING稳定性和激活的关键机制.
- 在调节STING功能方面,ISGylation和ubiquitination通路是相互连接的.
- 这项研究揭示了一种新的抗病毒机制,也是针对病毒感染的治疗干预的目标.
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