艾滋病毒Vpr激活了一个核细胞特异的ATR通路,以降低核细胞应激传感器CCDC1377
Karly A Nisson1, Rishi S Patel2, Yennifer Delgado1
1Molecular Biology Institute, University of California, Los Angeles, CA, 90095, United States.
Nucleic acids research
|June 18, 2025
概括
病毒蛋白Vpr通过降解CCDC137,一种感知核干扰的蛋白质,引起核应激. 这种Vpr诱导的核细胞应激会影响核糖体生物发生和细胞通路.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 病毒蛋白Vpr与细胞通路相互作用,导致宿主产生诸如DNA损伤反应 (DDR) 和G2/M停止等后果.
- 通过Vpr影响这些通路并影响其他细胞过程的精确机制仍然不完全理解.
研究的目的:
- 通过检查Vpr介导的核蛋白CCDC137.7的耗尽,研究Vpr诱导的DDR激活如何影响核细胞过程.
- 描述CCDC137降解在Vpr更广泛的细胞效应中的作用.
主要方法:
- 描述CCDC137作为一个间接的Vpr目标.
- 在对Vpr和基因组侮辱的反应中分析CCDC137降解.
- 核细胞应激标记的评估,包括蛋白质再分配,形态变化和核糖体生物发生,在Vpr.
- 研究ATR通路在Vpr诱导的核应激中的参与.
主要成果:
- CCDC137是一种间接的Vpr标,其降解与Vpr诱导的G2/M停止没有相关性.
- CCDC137的降解在不同的lentiviral Vpr蛋白中保存,并由基因组侮辱激活核细胞ATR通路而触发.
- Vpr诱导ATR依赖的核细胞应激,其特征是核细胞蛋白重新分配,改变形态和抑制的核糖体生物发生,这与CCDC137降解相关.
结论:
- CCDC137作为非正规的Vpr目标,并可能作为核细胞中断的传感器.
- 在诱导核应激方面,Vpr起着新的作用,通过CCDC137降解和ATR通路激活,影响核糖体生物发生和细胞功能.
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