通过PRMT1介导的氨酸甲基化促进了YAP的激活和肝细胞癌的扩散
Jian Yu1, Beibei Yu1, Zushun Peng1
1Xiangshan First People's Hospital Medical and Health Group, The Affiliated Xiangshan Hospital of Wenzhou Medical University, Luzhou, China.
FEBS open bio
|October 5, 2024
概括
氨基甲基转移酶PRMT1通过在R124.4上甲基化YAP来促进肝细胞癌 (HCC) 的生长. 这种甲基化抑制YAP酸化,增强其核活性,促进HCC瘤发生.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
背景情况:
- 河马信号通路及其效应器YAP在肝细胞癌 (HCC) 中经常受到失调.
- YAP活性是通过翻译后修饰来调节的,但阿金甲基化的作用尚不清楚.
研究的目的:
- 调查HCC.中阿尔金因甲基化对YAP调节的机制.
- 为了确定YAP上的特定的阿尔金宁甲基化位点.
- 确定PRMT1在YAP甲基化和HCC进展中的作用.
主要方法:
- 免疫沉和质谱测量以确定YAP甲基化位点.
- 实时qPCR和免疫光检测用于YAP/TEAD转录活性.
- 在体内研究使用皮下和正管瘤小鼠模型来评估PRMT1对HCC生长的影响.
主要成果:
- 质谱学确定了YAP甲基化在氨酸124 (R124) 的情况.
- PRMT1与YAP相互作用,调解R124氨酸甲基化,抑制YAP S127酸化,并促进核YAP活动.
- 在HCC组织中,PRMT1被上调,与YAP目标基因表达相关.
- 抑制PRMT1抑制HCC细胞增殖和瘤生长;过度表达PRMT1通过YAP甲基化促进HCC生长.
结论:
- 在R124中通过PRMT1介导的氨酸甲基化与YAP S127酸化是相互排斥的.
- 这种机制增强了YAP的核活性,促进了HCC的瘤发生.
- PRMT1是HCC的潜在治疗标.
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