在对DNA损伤的核突反应中,p73受氨酸激酶c-Abl的调节
1Department of Cancer Cell Biology, Harvard School of Public Health, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Nature
|July 3, 1999
概括
氨酸激酶c-Abl结合并酸化p73蛋白质,刺激其在亡中的作用. 这种相互作用对DNA损伤引起的细胞死亡至关重要,突出显示了p73.3的新调节途径.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 在瘤学瘤学.
背景情况:
- p73是p53瘤抑制剂的同类物,但不是由DNA损伤引起的.
- 氨酸激酶c-Abl被DNA损伤激活,并通过p53-依赖和独立的途径促进亡.
研究的目的:
- 研究c-Abl与p73.3之间的相互作用.
- 为了确定c-Abl是否调节p73的活性,以应对DNA损伤.
主要方法:
- 同免疫沉检测细胞中的c-Abl/p73结合.
- 使用电离辐射进行体外和细胞内酸化试验.
- 测试测量p73-介导的交换活化和亡.
主要成果:
- c-Abl通过其SH3域和p73的碳基末端域与p73结合.
- 在对电离辐射的反应中,c-Abl 在氨酸99处酸化p73.
- c-Abl增强了p73介导的交换活化和亡.
- 破坏c-Abl-p73相互作用会损害电离辐射诱导的亡.
结论:
- p73是由一个c-Abl-依赖的机制调节的.
- p73在对DNA损伤的亡反应中起作用.
- 这种c-Abl-p73相互作用对DNA损伤诱导的亡至关重要.
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