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快速接近标签系统PhastID将ATP6AP1识别为Rheb的一种非常规GEF

Ran Feng^1,2, Feng Liu³, Ruofei Li¹

¹MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, Guangzhou Key Laboratory of Healthy Aging Research, School of Life Sciences, Institute of Healthy Aging Research, Sun Yat-sen University, Guangzhou, Guangdong, China.

|March 6, 2024

概括

研究人员确定ATP6AP1是一种关氨酸核酸交换因子 (GEF),激活Rheb,这是mTORC1信号传输中的关键蛋白质. 这一发现澄清了Rheb激活,并为癌症提供了新的治疗点.

科学领域:

蜂信号传输是如何进行的
分子生物学分子生物学
生物化学生物化学

背景情况:

雷布是一种小G蛋白,激活mTORC1,对于营养和生长因子信号传递至关重要.
激活Rheb的特定关氨酸核酸交换因子 (GEF) 由于短暂的蛋白质-蛋白质相互作用而仍然难以捉摸.

研究的目的:

开发一种新的近距离标记系统 (PhastID),用于绘制临时蛋白质与蛋白质相互作用的地图.
确定负责Rheb激活的GEF并阐明其机制.

主要方法:

开发PhastID,一个由Pyrococcus horikoshii生物素蛋白联酶 (PhBPL) 辅助的生物素识别系统.
在活细胞中使用PhastID对胰岛素刺激的Rheb近距离蛋白网络的分析.

主要成果:

确定ATP6AP1是一种与Rheb.AP1动态相互作用的蛋白质.
证明ATP6AP1通过其C尾直接结合Rheb并增强Rheb的GTP负载.
表明向ATP6AP1的C尾抑制了癌细胞的增殖和迁移.

结论:

ATP6AP1作为Rheb的非传统GEF功能,填补了了解mTORC1通路激活的关键差距.
PhastID是一种多功能工具,用于研究活细胞中短暂的蛋白质-蛋白质相互作用.
ATP6AP1对于整合通过Rheb激活mTORC1的信号很重要,并且代表了癌症的潜在治疗标.

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