CDH1 编排合成代谢事件以促进细胞周期启动
Yun-Zi Mao1, Jiao-Jiao Zhang1,2, Meng-Qi You1
1The Obstetrics and Gynecology Hospital of Fudan University, Shanghai Key Lab of Reproduction and Development, Shanghai Key Lab of Female Reproductive Endocrine Related Diseases, Shanghai Key Laboratory of Metabolic Remodeling and Health, State Key Laboratory of Genetics and Development of Complex Phenotypes, and Institutes of Biomedical Sciences, Fudan Unviersity, Shanghai, 200433, China.
细胞循环调节器CDH1通过控制代谢,激活HIF1α进行代谢和AARS2以节约资源来协调细胞生长,从而促进细胞增殖和癌症进展.
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:
- 细胞增殖需要合成代谢过程,但合成代谢与细胞循环的整合仍然不清楚.
- 了解细胞是如何启动增殖的,需要研究代谢途径与细胞周期进展的协调.
研究的目的:
- 阐明G1阶段调节器CDH1在协调细胞周期启动的合成代谢事件中的作用.
- 确定CDH1在细胞周期进展过程中影响新陈代谢和合成物水平的分子机制.
主要方法:
- 研究了由CDH1.1降解希佩尔-林道 (VHL) 的降解.
- 分析了通过CDH1.1激活缺氧诱导因子1α (HIF1α) 和阿兰tRNA合成酶 (AARS2) 的活性.
- 研究了核糖-5-酸盐 (R5P) 与转基因酶样-1 (TKTL1) 的相互作用及其在CDH1调节中的作用.
主要成果:
- CDH1降解VHL,激活HIF1α以促进葡萄糖代谢和血管生成.
- CDH1激活AARS2,导致pyruvate脱酶E1亚单元α1 (PDHA1) 的失活,并保护了类合成物质.
- 由于CDH1活动而积累的R5P结合TKTL1,将CDH1桥接到CDK2和SCFβ-TRCP进行CDH1酸化和降解,促进细胞循环启动.
- 低R5P和高CDH1表达与癌细胞增殖相关.
- 人工R5P (R5S) 通过启动细胞周期而诱导癌细胞的亡.
结论:
- CDH1充当了细胞代谢的中心协调者,以确保细胞循环的启动.
- 已识别的CDH1-VHL-HIF1α/AARS2-R5P/TKTL1电路对细胞增殖至关重要,并与Warburg效应和血管生成等癌症特征有关.
- 针对这种电路为癌症治疗提供了潜在的治疗策略.
更多相关视频
08:33Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis
Published on: December 5, 2017
13:15Experimental Approaches to Study Mitochondrial Localization and Function of a Nuclear Cell Cycle Kinase, Cdk1
Published on: February 25, 2016
相关概念视频
Positive Regulator Molecules
Positive Regulator Molecules
Inhibition of Cdk Activity
M-Cdk Drives Transition Into Mitosis
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
The Cell Cycle Control System
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and...
The Cell Cycle Control System
