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通过mTOR对GCN2的酸化使其适应在压力下激活超mTOR的条件

Odai Darawshi¹, Olaya Yassin¹, Miri Shmuel¹

¹The School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel.

The Journal of biological chemistry

|July 16, 2024

概括

细胞通过综合应激反应 (ISR) 和机械点拉巴胺素 (mTOR) 途径适应氨基酸 (AA) 缺乏. 我们发现mTOR直接激活GCN2,在AA饥饿期间提高细胞存活率.

科学领域:

细胞生物学细胞生物学
分子生物学分子生物学
生物化学生化学

背景情况:

氨基酸 (AA) 缺乏引发综合应激反应 (ISR) 和机械标拉巴胺素 (mTOR) 途径,以调节细胞适应.
mTORC1抑制翻译启动和延伸,而ISR由GCN2激活,减少一般翻译,并诱导像ATF4.4这样的压力蛋白.

研究的目的:

确定ISR和mTORC1通路之间的新型交叉通话机制,以优化在AA饥饿期间的生存.
为了阐明mTORC1如何保持活跃并影响ISR信号在急性AA短缺的情况下.

主要方法:

在AA饥饿条件下研究了GCN2和mTORC1信号之间的相互作用.
利用生物化学分析来确定GCN2和mTOR之间的物理相互作用和酸化事件.
评估了GCN2酸化在长时间AA饥饿期间对细胞存活的功能影响.

主要成果:

发现了一种新型的交叉通话机制,在急性AA短缺期间,活跃的mTORC1以GCN2-依赖的方式增强ATF4表达.
确定了GCN2和mTOR之间的直接,不稳定的物理相互作用,导致mTOR介导的GCN2在230.0血清中的酸化.
证明mTOR诱导的GCN2酸化在长时间的AA饥饿下促进细胞存活.

结论:

揭示了一种新的适应机制,mTORC1通过直接激活GCN2来逃避AA饥饿期间的抑制.
通过mTOR介导的GCN2酸化是优化在营养应激下细胞存活的关键事件.
这种交叉沟通提供了生存优势,尽管缺乏营养素,但仍然保持了必要的应激反应.

关键词:

蛋白质对接的对接方式蛋白质蛋白质相互作用饥饿饥饿饥饿饥饿饥饿压力就是压力,压力就是压力.翻译法规翻译法规

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