2016年6月14日 · Our data establish that GCN2 is involved in the inhibition of mTORC1 upon leucine or arginine deprivation. However, the activation of GCN2 alone is not sufficient to inhibit mTORC1 activity,...

2023年12月5日 · Mammalian target of rapamycin complex 1 (mTORC1) monitors cellular amino acid changes for function, but the molecular mediators of this process remain to be fully defined. Here, we report that depletion of cellular amino acids, either alone or in combination, leads to the ubiquitination of mTOR, whi …

2023年12月5日 · Herein, we identify a novel amino-acid-sensing mechanism of mTORC1 that utilizes uncharged transfer RNA (tRNA)-mediated general control nonderepressible 2 (GCN2) activation to augment the F-box only protein 22 (FBXO22) activity for mTOR ubiquitination and mTORC1 inhibition.

2024年8月1日 · We identified a labile physical interaction between GCN2 and mTOR that results in a phosphorylation of GCN2 on serine 230 by mTOR, which promotes GCN2 activity. When examined under prolonged AA starvation, GCN2 phosphorylation by mTOR promoted survival. Our data unveils an adaptive mechanism to AA starvation, when mTORC1 evades inhibition.

2023年11月19日 · 该研究首次发现细胞内各种氨基酸浓度的改变可以统一地通过mTOR泛素化来被细胞感知，并进一步在机制上详细解释了mTORC1广泛感知所有氨基酸浓度波动的原理。 我们知道，每一种氨基酸均有其对应的转运RNA（tRNA），在其相应氨基酸充足的条件下，被氨酰tRNA合成酶催化形成氨酰tRNA。 如果氨基酸缺失，非氨酰化的tRNA（uncharged tRNA）将累积，并快速激活GCN2激酶。 活化的GCN2直接磷酸化位于FBXO22核定位信号邻位的T127位 …

2017年9月1日 · GCN2路径能有效感应胞内氨基酸缺乏，而mTORC1路径则能对胞外氨基酸水平的变化做出响应。 本文结合近年来有关GCN2和mTORC1的研究进展，阐述了氨基酸充足和氨基酸饥饿条件下，GCN2和mTORC1这两条信号路径的感应特点以及随后启动的相关应答机制，包括蛋白质合成、拒食行为、氨基酸转运体表达增加、氨基酸合成酶增加和自噬启动等。 了解动物在不同的氨基酸营养状态下维持细胞内氨基酸平衡的这些调节机制，有助于人们更好的对动物进行氮营 …

2016年12月14日 · 雷帕霉素靶蛋白 (mtor) 和一般性调控阻遏蛋白激酶 2(gcn2) 作为重要的信号转导分子，位于蛋白质合成与降解过程中整个信号通路的中心位点，是调控该过程的重要通路，并对蛋白质功能与作用的表达起到至关重要的作用。

We also discuss the antagonism of GCN2 and mTOR pathways in immune cells. A better understanding of GCN2′s functions and signaling pathways in the immune system under physiological, stressful, and pathological situations will be beneficial to the development of potential therapies for many immune-relevant diseases.

2023年12月15日 · Depletion of GCN2 abolished amino acid depletion-induced mTOR ubiquitination and FBXO22 translocation. Mechanistically, GCN2 could directly phosphorylate FBXO22 at Thr127, a process that can...

We identified a labile physical interaction between GCN2 and mTOR that results in a phosphorylation of GCN2 on serine 230 by mTOR, which promotes GCN2 activity. When examined under prolonged AA starvation, GCN2 phosphorylation by mTOR promoted survival. Our data unveils an adaptive mechanism to AA starvation, when mTORC1 evades inhibition.