在DNA受损后,ATM启动了E3泛基因酶COP1的自降解
David Dornan1, Harumi Shimizu, Angie Mah
1Department of Physiological Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
概括
在DNA损伤后,阿塔克西亚铁朗格iectasia突变 (ATM) 蛋白激酶调节COP1-p53轴. 在Ser(387) 上的COP1的ATM酸化破坏了COP1-p53的结合,稳定了p53及其瘤抑制功能.
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突变 (ATM) 蛋白激酶对DNA损伤反应和基因组完整性至关重要.
- 瘤抑制蛋白p53的稳定性由包括COP1在内的E3泛素连接酶调节,但ATM调节的途径尚不清楚.
研究的目的:
- 阐明在DNA损伤后调节COP1-p53轴的信号传导路径.
- 调查ATM在COP1和p53.3规范中的作用.
主要方法:
- 研究了DNA损伤对ATM,COP1和p53相互作用和定位的影响.
- 利用电离辐射诱导DNA损伤,并分析了COP1酸化在Ser387).
主要成果:
- 作为对DNA损伤的反应,ATM在Ser{387}上化COP1,触发COP1自降解.
- 电离辐射诱导了ATM依赖的COP1.1的核-细胞质转移.
- 通过ATM对Ser (387) 上的COP1的酸化破坏了COP1-p53复合体,防止了p53的无处不在和降解.
结论:
- 在DNA损伤后,p53稳定和瘤抑制活性是必不可少的.
- 这一途径代表了一种新的机制,用于调节p53功能,以应对基因组压力.
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