昼夜钟蛋白Cryptochrome 1是Hippo路径的直接目标和反调节器
Abdelhalim Azzi1, Zhipeng Tao1, Yang Sun1
1Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
iScience
|August 18, 2023
概括
昼夜时钟基因CRY1是由河马路的YAP蛋白调节的. 反过来,CRY1影响YAP活动,形成一个影响细胞生长和日常节律的网络.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 时间生物学 时间生物学
背景情况:
- 生物钟控制着每天的生理和行为模式.
- 信号通路影响核心时钟基因的表达.
- 河马通路是器官大小和细胞增殖的关键调节者.
研究的目的:
- 为了研究Hippo路径和核心昼夜钟基因CRY1.1之间的调节关系.
- 阐明YAP,Hippo通路效应器和CRY1转录之间的机械联系.
- 了解CRY1和Hippo路径组件之间的相互调节.
主要方法:
- 对YAP与CRY1促进体结合的分析.
- 对CRY1和YAP/TAZ表达水平的定量评估.
- 使用细胞模型研究CRY1在Hippo通路激活中的作用.
- 检查具有改变CRY1水平的乳腺癌细胞中的YAP/TAZ活性和DNA损伤.
主要成果:
- YAP直接与CRY1促进体结合,驱动其转录.
- 通过调节YAP和MOB1表达,CRY1对Hippo路径激活产生负反.
- CRY1的丧失导致YAP激活的增加和时钟基因振荡的失调.
- 乳腺癌细胞中CRY1的下调导致YAP/TAZ过活化和DNA损伤增加.
结论:
- 河马路径和昼夜时钟之间存在直接的机械联系.
- CRY1和Hippo通路组件形成了一个集成的网络,调节细胞生长和昼夜节律.
- 这种交叉通话对了解细胞过程和癌症等疾病有影响.
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