通过增加糖分来启动细胞循环:mTOR在APC/C-CDH1上的制动触发了糖分分解脉冲
1School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
Developmental cell
|October 7, 2025
概括
退出静止状态的细胞需要复制DNA并促进新陈代谢. 基因激活的mTOR暂时抑制APC/C-CDH1,激活PFKFB3进行能量激增,从而启动细胞增殖.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 代谢过程中的代谢.
背景情况:
- 细胞静止是一种可逆细胞循环停止的状态.
- 退出静止需要协调的代谢和DNA复制准备.
- 具有Cdh1 (APC/C-CDH1) 的亚纳促进复合体/循环体 (APC/C) 是细胞循环进展的关键调节者.
研究的目的:
- 研究将细胞周期从静止状态到代谢激活的分子机制.
- 阐明mTOR信号在细胞循环重新进入期间调节代谢酶中的作用.
- 了解APC/C-CDH1活动如何在从静止到扩散的过渡过程中受到调节.
主要方法:
- 静止和增殖的细胞培养模型.
- 西方斑点测试用于评估蛋白质含量和酸化.
- 定量实时PCR用于基因表达分析.
- 代谢测试用于测量糖解速率.
主要成果:
- 基因刺激激活了mTOR信号传递.
- 激活的mTOR暂时抑制了APC/C-CDH1.1的活性.
- 这种抑制导致6-果糖-2-激酶/果糖-2,6-双酸酶3 (PFKFB3) 的上调,这是一个关键的糖解酶.
- 增加的PFKFB3活性会促进糖解,提供ATP进行增殖.
- 后来APC/C-CDH1活动恢复,促进细胞循环的进展.
结论:
- 通过mTOR暂时抑制APC/C-CDH1,这对于静止退出期间的代谢重编程至关重要.
- PFKFB3充当关键的调解者,将细胞循环控制与代谢支持的增殖联系起来.
- 这个调节轴确保细胞在承诺DNA复制之前有足够的能量.
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