STING是一种内质网膜适配器,可促进先天免疫信号传递
Hiroki Ishikawa1, Glen N Barber
1Department of Medicine and Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, Florida 33136, USA.
Nature
|August 30, 2008
概括
研究人员确定了一个关键分子,干扰素基因刺激器 (STING),对抗病毒感染的先天免疫反应至关重要. 刺激活会触发抗病毒防御,而缺少它会增加对病毒和DNA病原体的易感性.
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:
- 细胞天生的免疫系统对于病原体的识别和宿主防御至关重要.
- 天生的免疫力中的关键分子参与者,特别是对抗DNA和RNA病毒的关键分子参与者,尚未完全理解.
研究的目的:
- 为了确定新型的分子决定因素,对于先天免疫信号通路至关重要.
- 阐明新发现的分子在抗病毒反应中的作用.
主要方法:
- 表达式克隆用于识别STING分子.
- 分析了NF-kappaB和IRF3的转录途径.
- 进行了酵母双杂交和共免疫沉研究.
- 使用RNA干扰来消去TRAPbeta和SEC61beta.
主要成果:
- 细胞内膜网中的跨膜蛋白STING激活NF-kappaB和IRF3,诱导I型干扰素 (IFN-alpha,IFN-beta) 和抗病毒状态.
- 失去STING增加了对负链RNA病毒的敏感性.
- 刺切除损害了细胞内DNA和疹病毒的IFN-β诱导,但没有TLR信号传导.
- STING 与 RIG-I 和 TRAPbeta 相互作用,而 TRAPbeta/SEC61beta 除抑制了 STING 介导的 IFN-β 诱导.
结论:
- STING是先天免疫信号的关键调节者,对抗病毒防御至关重要.
- 转位子复合体可能在病毒和细胞内DNA激活的先天免疫信号通路中发挥作用.
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