泰尔2调节PI3K相关蛋白激酶的稳定性
Hiroyuki Takai1, Richard C Wang, Kaori K Takai
1Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Cell
|December 28, 2007
概括
泰尔2对于维持所有哺乳动物酸丁酸3-酶相关蛋白酶 (PIKKs) 的稳定性至关重要. 这一发现揭示了Tel2的存在.
科学领域:
- 细胞和分子生物学 细胞和分子生物学
- 遗传学和基因组学 在
- 生物化学 生物化学
背景情况:
- Tel2最初在酵母中被鉴定为其在端粒维护中的作用.
- 哺乳动物Tel2缺乏明显的端粒功能,但对胚胎发育至关重要.
- Tel2影响细胞对DNA损伤的反应,包括检查点激酶激活.
研究的目的:
- 研究Tel2在哺乳动物细胞中的功能.
- 确定Tel2删除对脂氨基醇3-酶相关蛋白酶 (PIKKs) 的影响.
- 阐明Tel2调节PIKKs的机制.
主要方法:
- 针对性基因删除在小鼠和胚胎纤维细胞中.
- 在胚胎纤维细胞中条件删除Tel2.
- 对PIKK蛋白水平,mRNA表达和信号通路的分析.
- 在体内进行脉冲标记和共免疫沉试验.
主要成果:
- 在胚胎发育过程中,tel2删除是致命的,并且会损害纤维细胞中的DNA损伤反应.
- 失去Tel2导致所有六种哺乳动物PIKK的蛋白质水平显著降低,包括ATM,ATR,DNA-PKcs,mTOR,SMG1和TRRAP.
- Tel2控制的是ATM和mTOR的稳定性,而不是mRNA水平.
- Tel2直接与ATM和mTOR结合在一起.
结论:
- 泰尔2是哺乳动物PIKK稳定的重要调节剂.
- 泰尔2在控制PIKK家族蛋白质水平方面起着保留作用.
- 这一发现突出了Tel2作为细胞信号传递和DNA修复途径的关键因素.
相关概念视频
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