基线展开的蛋白质反应信号调整了哺乳动物细胞周期的时间
Soham P Chowdhury1, Sabrina C Solley1, Elena Polishchuk2
1Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106.
Molecular biology of the cell
|April 24, 2024
概括
细胞分裂需要维持内质网膜 (ER). 展开蛋白质响应 (UPR) 信号,特别是PERK,影响细胞周期进展和线粒分裂前的ER扩大,确保有机体遗传.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 机体生物学 机体生物学
背景情况:
- 细胞内膜网膜 (ER) 对于细胞功能至关重要,不能重新创建.
- 在细胞分裂期间保持ER完整性对于有机细胞遗传至关重要.
- 展开的蛋白质反应 (UPR) 是ER恒温的关键调节者.
研究的目的:
- 研究UPR信号与细胞循环之间的协调.
- 确定UPR传感器 (IRE1,ATF6,PERK) 在细胞周期进展中的作用.
- 了解如何在细胞分裂过程中维持ER稳态.
主要方法:
- UPR传感器的药理和遗传抑制 (IRE1,ATF6,PERK).
- 使用流细胞计进行细胞周期分析.
- 显微镜 (光和电子) 来评估ER形态.
- 用ISRIB进行治疗,以调查eIF2α酸化效应.
主要成果:
- 抑制UPR传感器,特别是PERK,延迟细胞循环,特别是G1-to-S/G2过渡.
- PERK的激酶活性,而不是eIF2α酸化,对于细胞周期计时至关重要.
- 在发生线粒分裂之前,ER会经历显著扩大.
- UPR信号与细胞周期协调,以管理ER生理学.
结论:
- UPR信号通路与细胞循环控制机制相结合.
- 珀克在调节细胞周期进展和ER动态方面发挥着至关重要的作用.
- 这种协调确保了适当的ER遗传和细胞功能.
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