能量状态协调YTHDF1相分离和瘤发生
Haisheng Yu1, Jie Shi1, Rongrong He2
1Department of Radiation and Medical Oncology, State Key Laboratory of Metabolism and Regulation in Complex Organisms, Medical Research Institute, Frontier Science Center of Immunology and Metabolism, Hubei Key Laboratory of Tumor Biological Behavior, Hubei Provincial Clinical Research Center for Cancer, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China; Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan 430071, China.
细胞能量状态通过腺单酸盐 (AMP) 激活的蛋白激酶 (AMPK) 信号影响癌症. 用AMPK激动剂或性饮食向YTHDF1修饰抑制瘤生长,提供新的癌症治疗策略.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 异常的细胞能量代谢与瘤发生有关,但机制尚不清楚.
- 氨酸单酸 (AMP) 激活蛋白激酶 (AMPK) 感知能量压力并调节癌症.
- YTHDF1蛋白质的修改与癌症进展有关.
研究的目的:
- 调查AMPK在调节YTHDF1后翻译修改中的作用.
- 阐明这些修改如何影响YTHDF1功能和蛋白质翻译.
- 探索在癌症中准这种途径的治疗潜力.
主要方法:
- 研究了能源剥夺诱导的AMPK激活.
- 分析了YTHDF1.1的酸化和O-GlcNAcylation.
- 评估了YTHDF1相隔离和与eIF3b.b的相互作用.
- 在体外和体内使用AMPK激动剂和性饮食对瘤细胞生长抑制进行了评估.
主要成果:
- AMPK激活酸化YTHDF1在Ser198处,抵消其O-GlcNAcylation的作用.
- YTHDF1酸化抑制相分离和eIF3b相互作用,减少蛋白质翻译.
- AMPK激动剂和性饮食通过增强YTHDF1酸化来抑制瘤细胞的生长.
结论:
- 一个新的机制将细胞能量状态与YTHDF1修饰和蛋白质翻译联系起来.
- 通过代谢干预来准YTHDF1的翻译后修改显示了癌症的治疗前景.
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