PABPC1 SUMOylation通过稳定压力颗粒中的富含U的mRNA来促进细胞食,从而提高细胞存活率
Caihu Huang1,2, Jiayi Huang1, Runhui Lu1
1Department of Biochemistry and Molecular Cell Biology & Department of Thoracic Surgery Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Nature communications
|August 7, 2025
概括
聚A结合蛋白细胞质蛋白1 (PABPC1) SUMOylation驱动压力颗粒组装,通过稳定特定的mRNAs来增强癌细胞存活率. 这种机制通过选择性mRNA调节和线粒细胞衰变促进了对压力的适应.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 压力颗粒 (SGs) 通过调节mRNA代谢,对细胞适应压力至关重要.
- 在压力下,SGs在癌细胞生存中的确切作用尚未完全理解.
- 聚A结合蛋白细胞质蛋白1 (PABPC1) 是压力颗粒的已知组成部分.
研究的目的:
- 研究PABPC1修饰在压力颗粒形成和癌细胞存活中的作用.
- 确定压力颗粒促进癌细胞适应的分子机制.
- 探索PABPC1,压力颗粒和压力下的特定基因表达之间的联系.
主要方法:
- 确定PABPC1作为一种应力诱导的SUMOylation标.
- 全转录组分析以确定稳定的mRNAs.
- 生物化学测试以表征PABPC1-SUMO-TIA1复合体及其与RNA的相互作用.
主要成果:
- PABPC1的SUMOylation促进了压力颗粒的组装,并增强了癌细胞在压力下的生存率.
- SUMOylated PABPC1 选择性地稳定含有 U 丰富元素的 mRNA.
- PABPC1-SUMO-TIA1复合体将富含U的mRNA招募到压力颗粒中,保护它们免受降解.
- 这种稳定促进了与线粒细胞衰变相关的基因的表达,支持细胞平衡.
结论:
- PABPC1 SUMOylation 是压力颗粒组装和功能的关键调节者.
- SUMOylated PABPC1通过选择性稳定参与线粒细胞衰变的富含U的mRNA来促进癌细胞的存活.
- 这一途径突出了癌细胞适应压力的新机制.
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