在细胞循环进入过程中,mTOR 暂时的APC/C 失活会促进糖分分解
Debasish Paul1, Derek L Bolhuis2,3, Hualong Yan1
1Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Nature
|July 31, 2025
概括
进入细胞循环的哺乳动物细胞暂时失活了亚纳促进复合体/循环体 (APC/C),以促进糖解. 这种代谢转变支持细胞分裂的快速生物质积累.
科学领域:
- 细胞生物学
- 代谢过程
- 生物化学
背景情况:
- 细胞循环进入需要快速的ATP和生物合成,有利于糖解.
- 亚纳相促进复合体/循环体 (APC/C) 调节细胞分裂,但矛盾的是抑制糖解.
- 细胞周期和新陈代谢的协调调节对于细胞分裂至关重要.
研究的目的:
- 研究哺乳动物细胞如何与代谢需求协调细胞循环的进入.
- 阐明细胞循环进展过程中尽管有APC/C活性,但仍有利于糖解的机制.
主要方法:
- 研究了APC/C^CDH1活性在细胞循环进入期间调节糖分的作用.
- 使用哺乳动物细胞模型研究对APC/C和糖解酶水平的影响.
- 研究了mTOR介导的CDH1化对APC/ C功能和PFKFB3积累的影响.
主要成果:
- 在细胞循环进入过程中,APC/C的暂时失活使代谢转向糖解.
- 基因刺激会触发mTOR介导的CDH1酸化,导致部分APC/ C无活化.
- 这种无活化稳定了PFKFB3,一个关键的糖解酶,增强了生物质生产的糖解.
结论:
- 细胞采用不连贯的前进循环,涉及暂时的APC/C抑制,以产生细胞循环进入的糖解脉冲.
- 这种机制确保了足够的ATP和生物合成中间体,以实现快速的细胞增殖.
- 这项研究揭示了细胞周期进展和细胞代谢之间的新协调策略.
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