生物
蛋白酶体
PI3K/AKT/mTOR通路
细胞生物学
胞浆
TFEB
分区(防火)
自噬
雷帕霉素的作用靶点
泛素
氨基酸
转录因子
蛋白质降解
蛋白质水解
生物化学
信号转导
细胞凋亡
基因
酶
作者
Ido Livneh,Victoria Cohen‐Kaplan,Bertrand Fabre,Ifat Abramovitch,Lulu Chen,Nishanth Belugali Nataraj,Ikrame Lazar,Tamar Ziv,Yosef Yarden,Yaniv Zohar,Eyal Gottlieb,Aaron Ciechanover
出处
期刊:Molecular Cell
[Elsevier]
日期:2023-09-01
卷期号:83 (18): 3333-3346.e5
被引量:1
标识
DOI:10.1016/j.molcel.2023.08.016
摘要
The proteasome is responsible for removal of ubiquitinated proteins. Although several aspects of its regulation (e.g., assembly, composition, and post-translational modifications) have been unraveled, studying its adaptive compartmentalization in response to stress is just starting to emerge. We found that following amino acid starvation, the proteasome is translocated from its large nuclear pool to the cytoplasm-a response regulated by newly identified mTOR-agonistic amino acids-Tyr, Trp, and Phe (YWF). YWF relay their signal upstream of mTOR through Sestrin3 by disrupting its interaction with the GATOR2 complex. The triad activates mTOR toward its downstream substrates p62 and transcription factor EB (TFEB), affecting both proteasomal and autophagic activities. Proteasome translocation stimulates cytosolic proteolysis which replenishes amino acids, thus enabling cell survival. In contrast, nuclear sequestration of the proteasome following mTOR activation by YWF inhibits this proteolytic adaptive mechanism, leading to cell death, which establishes this newly identified pathway as a key stress-coping mechanism.
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