线性ubiquitination调节KSHV复制和转录激活蛋白,以控制感染
Yi Luan1,2,3,4, Wenying Long5, Lisi Dai6,7,8
1Clinical Systems Biology Laboratories, Translational Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Nature communications
|July 1, 2024
概括
线性ubiquitination调节KSHV RTA蛋白在病毒再激活期间的活性. 奥图林蛋白抑制了这一过程,而HOIP则增强了这一过程,控制了RTA.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 无处不在生物学的生物学
背景情况:
- 卡波西的肉瘤相关性疹病毒 (KSHV) 呈现潜伏和流性生命周期阶段.
- KSHV RTA 蛋白对于启动溶解阶段至关重要,但其调节机制尚不清楚.
- 后翻译性修饰的ubiquitination在细胞过程中起到不同的作用,包括病毒感染.
研究的目的:
- 研究线性无化在调节KSHV RTA蛋白活性中的作用.
- 阐明线性无化控制KSHV光学反应的特定机制.
主要方法:
- 在KSHV感染细胞中,OTULIN和HOIP蛋白的过度表达和敲击.
- 分析RTA蛋白的泛化状态,特别是在K516和K518.
- 使用细胞和分子生物学技术评估RTA蛋白的核定位.
- 在爱斯坦-巴尔病毒 (EBV) 和子疹病毒68 (MHV68) 中对RTA正体的比较分析.
主要成果:
- 奥林的过度表达抑制了KSHV的催化反应,而奥林的淘汰或HOIP的过度表达增强了它.
- 在氨酸残留物K516和K518上,RTA的HOIP介导的线性聚基化.
- 发现这些无所不在的事件控制了RTA的核进口,OTULIN对细胞质RTA进行了deubiquitination.
- 来自EBV和MHV68的RTA骨科也表现出线性多基化和OTULIN-依赖调节.
结论:
- 线性多比基因化是一种关键的调节机制,在病毒再激活和感染期间控制KSHV RTA活性.
- HOIP和OTULIN之间的相互作用控制RTA的亚细胞局部化,因此,KSHV的Lytic复制.
- 这项研究突出了线性多基化在调节疹病毒感染中的保留作用.
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