在对DNA损伤的反应中,ATM蛋白和c-Abl之间的相互作用
T Shafman1, K K Khanna, P Kedar
1Joint Center for Radiation Therapy, Dana Farber Cancer Institutes, Boston, Massachusetts 02115, USA.
Nature
|May 29, 1997
概括
在DNA损伤的反应中,阿塔克西亚特朗吉克塔西亚突变 (ATM) 蛋白与c-Abl 氨酸激酶相互作用. 这种相互作用对于激活c-Abl和在暴露于辐射后调解G1/S细胞周期停止至关重要.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
背景情况:
- ATAxia telangiectasia (AT) 是一种由ATM基因突变引起的自体衰退性疾病.
- ATM是一种类似酸-3-酶的酶,参与DNA损伤反应和细胞循环控制.
- 亚特细胞对电离辐射过敏,G1/S检查点有缺陷.
研究的目的:
- 为了调查ATM和c-Abl在DNA损伤反应中的潜在相互作用.
- 阐明ATM在激活c-Abl氨酸激酶活性中的作用.
主要方法:
- 研究了ATM和c-Abl在控制和AT细胞中的结合.
- 通过蛋白质结合试验确定了ATM和c-Abl之间的特定相互作用动机.
- 评估了DNA损伤对AT细胞中c-Abl氨酸激酶活性的影响.
主要成果:
- 在正常细胞中,ATM以构成性方式与c-Abl结合,但在AT细胞中没有这种相互作用.
- 在ATM中,c-Abl的SH3域与特定的动机 (DPAPNPPHFP) 相互作用.
- 在AT细胞中,c-Abl氨酸激酶的辐射诱导激活显著减少.
结论:
- 在DNA损伤引起的c-Abl.激活过程中,ATM起着至关重要的作用.
- ATM和c-Abl之间的相互作用对于调解辐射诱导的G1/S细胞周期停止至关重要.
- 这些发现揭示了DNA损伤反应途径中的一种新机制.
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