通过可逆的YAP和对循环林D1/p27比率的线粒激素控制的过渡性增殖
Katherine R Ferrick1,2, Yilin Fan1,2,3, Nalin Ratnayeke1,2,4
1Department of Cell and Developmental Biology, Weill Cornell Medicine, New York, NY, USA.
bioRxiv : the preprint server for biology
|October 17, 2024
概括
在组织修复过程中,Hippo-YAP信号控制细胞增殖,通过调节环林D1/p27比率来控制细胞增殖. 这一途径集成了线粒原信号和接触抑制,这对于再生医学应用至关重要.
科学领域:
- 细胞生物学 细胞生物学
- 再生医学是一种再生医学.
- 分子生物学分子生物学
背景情况:
- Hippo-YAP信号对于上皮组织的修复至关重要,也是再生医学的关键目标.
- 在控制细胞增殖方面,YAP与线粒原信号传递和接触抑制的整合仍然不清楚.
研究的目的:
- 阐明YAP信号如何与基因信号和接触抑制相互作用,以调节组织修复期间的短暂增殖反应.
主要方法:
- 研究了YAP-TEAD激活在控制G1阶段核环林D1/p27蛋白比率中的作用.
- 研究了减少接触抑制和增加基因信号的对YAP活动的影响.
- 利用默林/NF2除来研究YAP在扩散控制和密度依赖调节中的作用.
主要成果:
- 减少接触抑制,增加基因信号传递和YAP-TEAD激活,共同提高核环林D1/p27比率,决定细胞周期的进入/退出.
- 通过对EGFR等通过ERK发出信号的受体进行上调,YAP间接地提高了这种比率,从而延长了增殖的时间.
- 接触抑制最终抑制了YAP活动,在延迟后降低了线粒原信号传递和环素D1/p27比率.
结论:
- 循环素D1/p27比率的YAP介导的,受体依赖的延长驱动了组织修复所必需的强大的增殖.
- 延迟抑制受体信号,在YAP的接触抑制之后,需要扭转这种增殖状态.
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