叉头转录因子有助于哺乳动物中线粒计划的执行
B Alvarez1, C Martínez-A, B M Burgering
1Department of Immunology and Oncology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, Madrid E-28049, Spain.
Nature
|October 19, 2001
概括
叉头转录因子 (FKH-TFs) 通过调节线粒基因来控制细胞循环的完成. 在G2中降低PI(3)K/PKB通路的调节对于FKH-TF激活和适当的细胞分裂至关重要.
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:
- 细胞周期的进展是由内部和外部信号,包括生长因子来调节的.
- PI(3)K/PKB通路对于细胞循环进入至关重要,因为它通过 G1 中的FKH-TFs的失活,使细胞循环进入至关重要.
- 细胞周期进展的内生控制发生在限制点之后.
研究的目的:
- 研究PI(3)K/PKB通路衰减在G2中的作用.
- 为了确定G2.2中的FKH-TF活动的功能.
- 阐明哺乳动物细胞周期终结的机制.
主要方法:
- 研究了PI(3)K/PKB通路调节对FKH-TF活性的影响.
- 利用转录不活跃的FKH突变来评估FKH-TF功能.
- 分析了细胞周期进展,细胞动力学和线粒基因表达 (cyclin B, Plk).
主要成果:
- 在G2中PI(3)K/PKB通路的减弱是FKH-TF转录激活所必需的.
- 干扰PI(3)K/PKB下调或FKH-TF活动导致G2/M停止,细胞动力学失败,并延迟M到G1的过渡.
- FKH-TFs调节关键的线粒基因的表达,包括环林B和波罗样酶 (Plk).
结论:
- FKH-TFs在控制哺乳动物细胞周期完成方面发挥着至关重要的作用.
- 有效的线粒细胞进展依赖于PI(3)K/PKB通路下调和随后的FKH转录活性.
- 这项研究揭示了细胞循环终结的新机制,涉及PI(3)K/PKB通路和FKH-TF活性的动态调节.
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