七素通过SOCS7介导的NCK的核积累来调节actin组织和细胞循环停止
Brandon E Kremer1, Laura A Adang, Ian G Macara
1Department of Microbiology, University of Virginia School of Medicine, Charlottesville, VA 22908-0577, USA.
Cell
|September 7, 2007
概括
哺乳动物的隔膜和SOCS7蛋白调节细胞极性和DNA损伤反应. 由SOCS7促进的NCK蛋白的核积累对于DNA损伤后的细胞循环停止至关重要.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 哺乳动物隔膜是GTP结合蛋白,其功能尚不清楚.
- Septin knockdown (SEPT2,6,7) 破坏了应力纤维和细胞极性.
- 适应蛋白NCK在隔膜功能和DNA损伤反应中的作用尚不清楚.
研究的目的:
- 为了研究septin-SOCS7-NCK轴在细胞对DNA损伤的反应中的作用.
- 阐明NCK影响细胞极性和细胞循环停止的机制.
- 为了确定隔膜,SOCS7,NCK和DNA损伤级联之间的联系.
主要方法:
- 研究了NCK局部化 (细胞质与核) 对细胞表型的影响.
- 利用SOCS7的核进出口信号来控制NCK的核入口.
- 在DNA损伤时检查了actin和septin的重新排列.
- 评估了NCK对细胞循环停止和p53酸化的影响.
主要成果:
- 由SOCS7介导的NCK的核积累诱导了观察到的隔膜淘汰表型.
- SOCS7促进NCK的核运输,并与septins和NCK相互作用.
- DNA 损伤触发了NCK和SOCS7的快速核积累,导致了actin和septin的重新排列.
- 对于DNA损伤引起的细胞循环停止和p53 Ser15酸化,NCK是必不可少的.
结论:
- 隔膜-SOCS7-NCK通路是细胞极性和DNA损伤反应的新型调节者.
- 这个轴在DNA损伤级联中的ATM/ATR激酶的下游运行.
- 七素,SOCS7和NCK信号相互连接,对保持基因组完整性至关重要.
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