阿克特通过酸化和抑制叉头转录因子促进细胞生存
A Brunet1, A Bonni, M J Zigmond
1Children's Hospital and Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Cell
|April 2, 1999
概括
生存因子通过调节转录因子FKHRL1.1来预防细胞死亡. 阿克特酸化使FKHRL1保持在细胞质中,但其缺失会触发核进入和亡.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 存活因子通过Akt激活,酸化BAD和Caspase 9来抑制亡.
- 氨酸/氨酸激酶Akt在细胞生存途径中起着至关重要的作用.
- 细胞亡,或编程细胞死亡,是一种严格调节的细胞过程.
研究的目的:
- 调查Akt在调节叉头转录因子FKHRL1.1中的作用.
- 阐明生存因素影响FKHRL1活动和局部化的机制.
- 确定FKHRL1对诱导亡的贡献.
主要方法:
- 西方涂抹检测蛋白质酸化.
- 免疫沉以研究蛋白质-蛋白质相互作用 (Akt,FKHRL1,14-3-3蛋白质).
- 亚细胞分离以确定FKHRL1的定位 (细胞质与核).
- 定量PCR和报告测试用于评估目标基因表达.
主要成果:
- 在存在生存因子的情况下,Akt酸化物FKHRL1.
- 化FKHRL1与14-3-3蛋白结合,并留在细胞质中.
- 脱离生存因子会导致FKHRL1脱,核转位和目标基因的激活.
- FKHRL1核转位与诱导亡有关,包括Fas联结体表达.
结论:
- 通过Akt介导的FKHRL1酸化是通过生存因子介导的亡抑制的关键机制.
- 在核转位时,FKHRL1充当了亲细胞亡的转录因子.
- 这一途径突出了控制细胞命运决策的新型调控轴.
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