基因酶ATM和NF-kappaB在对基因毒性刺激的反应中发出信号之间的分子联系
Zhao-Hui Wu1, Yuling Shi, Randal S Tibbetts
1Department of Pharmacology, University of Wisconsin-Madison, 301 SMI, 1300 University Avenue, Madison, WI 53706, USA.
概括
该NF-kappaB基本调节器 (NEMO) 蛋白与ATM和IKK信号通路相连. 这种相互作用激活NF-kappaB作为对DNA损伤的反应,影响细胞死亡途径.
科学领域:
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
- 对DNA损伤的反应反应
背景情况:
- 转录因子NF-kappaB在调节对基因毒性压力的亡反应中起着至关重要的作用.
- NF-kappaB信号传递受到IkappaB激酶 (IKK) 综合体的严格调节,该综合体包括NF-kappaB基本调节器 (NEMO) 子单元.
研究的目的:
- 阐明基因毒性压力激活NF-kappaB.B.的分子机制.
- 为了研究形电垂体突变 (ATM) 激酶在NEMO和NF-kappaB激活的调节中的作用.
主要方法:
- 同免疫沉试验用于研究ATM,NEMO和IKK之间的蛋白质与蛋白质相互作用.
- 西方涂抹检测NEMO的酸化和无处不在.
- 免疫光显微镜用于追踪ATM和NEMO的亚细胞局部.
主要成果:
- 在DNA双链断裂后,激活的ATM激酶与NEMO相关.
- ATM化了NEMO的赛林-85,促进了其核出口.
- NEMO促进了细胞质转移和激活IKK的ATM,涉及ELKS蛋白.
结论:
- 监管NEMO的核穿是连接ATM和IKK信号通道的关键事件.
- 这种依赖NEMO的机制在对基因毒性信号的反应中激活NF-kappaB,影响细胞命运.
- 这些发现为复杂的DNA损伤反应和NF-kappaB激活网络提供了新的见解.
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