ArticleMolecular cell2023
Regulation of nucleo-cytosolic 26S proteasome translocation by aromatic amino acids via mTOR is essential for cell survival under stress.
Article in Molecular cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed, 35 citations in OpenAlex.
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- The TRPM7 inhibitor carvacrol suppresses angiogenesis and vasculogenic mimicry in triple-negative breast cancer.International journal of biological sciences · 2026Article
- Nuclear-Cytoplasmic Axis in Cancer: From Protein Mislocalization to Anticancer Drug Resistance.Oncology research · 2026Review
- mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics.Signal transduction and targeted therapy · 2025Review
- Regulation via compartmentation: adaptive localization of the proteasome under stress.Biochemical Society transactions · 2025Review
- Lymphodepleting chemotherapy potentiates neoantigen-directed T cell therapy by enhancing antigen presentation.Cell reports. Medicine · 2025Article
- A C-terminal cytoplasmic retention motif and nuclear localization signal regulates nuclear import of TP53INP2.Journal of cell science · 2025Article
- Proteasomal activity and disease outcome in phenylketonuria patients with a structural SLC7A5 variant.Scientific reports · 2025Article
- Differential cell survival outcomes in response to diverse amino acid stress.Life science alliance · 2025Article
- Exploratory Insights into Gastric Cancer Metabolism Through Amino Acid and Acylcarnitine Profiling in Plasma Samples.Biomedicines · 2025Article
- Exercise-induced lactate suppresses ccRCC via CNDP2-mediated depletion of intracellular amino acids.Cell death discovery · 2025Article
- The flux of energy in critical illness and the obesity paradox.Physiological reviews · 2025Review
- Maize big embryo 6 reveals roles of plastidial and cytosolic prephenate aminotransferases in seed and plant development.The Plant cell · 2025Article
- Regulation of TFEB in human placental Cytotrophoblasts and Syncytiotrophoblasts.Physiological reports · 2025Article
- Aromatic Amino Acid Metabolites: Molecular Messengers Bridging Immune-Microbiota Communication.Immune network · 2025Review
- MLKL-USP7-UBA52 signaling is indispensable for autophagy in brain through maintaining ubiquitin homeostasis.Autophagy · 2025Article
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12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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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