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METTL13eEF1A的甲基化增加了转化输出以促进瘤发生
Shuo Liu1, Simone Hausmann2, Scott Moore Carlson1
1Department of Biology, Stanford University, Stanford, CA 94305, USA.
Cell
|January 8, 2019
概括
细胞延长因子1A的METTL13蛋白修饰增强了癌症的生长. 在Ras驱动的癌症中抑制METTL13和eEF1AK55me2会减少瘤的发展,并增加药物敏感性.
科学领域:
- 分子生物学
- 癌症学
- 生物化学
背景情况:
- 增加蛋白质合成对于癌症的发展至关重要.
- 拉斯驱动的癌症依赖于增强的转化输出来产生瘤.
研究的目的:
- 研究METTL13介导的eEF1A甲基化在Ras驱动的癌症中的作用.
- 探索METTL13-eEF1AK55me2作为一个潜在的治疗目标.
主要方法:
- 在体外测试以测量GTPase活性.
- 细胞测试以评估蛋白质的产生.
- 使用小鼠模型和患者衍生的异种移植 (PDX) 的体内研究.
主要成果:
- 在lysine 55 (eEF1AK55me2) 中对eEF1A的METTL13二甲基化增加了蛋白质合成并促进了瘤的生长.
- 高METTL13和eEF1AK55me2水平与胰腺癌和肺癌患者的生存率差相关.
- 在体内,METTL13删除或eEF1AK55me2损失显著抑制Ras驱动的瘤生长.
- METTL13的枯竭使瘤对向治疗产生敏感性.
结论:
- METTL13-eEF1AK55me2轴对于满足Ras驱动癌症的高蛋白合成需求至关重要.
- 针对METTL13代表了异常Ras信号的癌症的潜在治疗策略.
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