ArticleMolecular cell2020
Amino Acids Enhance Polyubiquitination of Rheb and Its Binding to mTORC1 by Blocking Lysosomal ATXN3 Deubiquitinase Activity.
Article in Molecular cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- Amino acid-dependent TSC2 dephosphorylation by lysosome-PP2A regulates mTORC1 signaling transduction.Life science alliance · 2025Article
- HUWE1 stimulates mTORC1 activity by enhancing Rheb interaction with mTORC1 and supports de novo pyrimidine synthesis.Cell reports · 2025Article
- Intracerebellar upregulation of Rheb(S16H) ameliorates motor dysfunction in mice with SCA2.Acta pharmacologica Sinica · 2025Article
- The Cullin3-Rbx1-KLHL9 E3 ubiquitin ligase complex ubiquitinates Rheb and supports amino acid-induced mTORC1 activation.Cell reports · 2025Article
- Article
- Glucose deprivation triggers DCAF1-mediated inactivation of Rheb-mTORC1 and promotes cancer cell survival.Cell death & disease · 2024Article
- Friend or foe? Reciprocal regulation between E3 ubiquitin ligases and deubiquitinases.Biochemical Society transactions · 2024Review
- GATOR1 Mutations Impair PI3 Kinase-Dependent Growth Factor Signaling Regulation of mTORC1.International journal of molecular sciences · 2024Article
- Coordinated Regulation of Myelination by Growth Factor and Amino-acid Signaling Pathways.Neuroscience bulletin · 2023Review
- Picornavirus infection enhances aspartate by the SLC38A8 transporter to promote viral replication.PLoS pathogens · 2023Article
- Sensory nerve niche regulates mesenchymal stem cell homeostasis via FGF/mTOR/autophagy axis.Nature communications · 2023Article
- Rag GTPases regulate cellular amino acid homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2022Review
- Lysosomes at the Crossroads of Cell Metabolism, Cell Cycle, and Stemness.International journal of molecular sciences · 2022Review
- How Cells Deal with the Fluctuating Environment: Autophagy Regulation under Stress in Yeast and Mammalian Systems.Antioxidants (Basel, Switzerland) · 2022Review
- GATOR2 complex-mediated amino acid signaling regulates brain myelination.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- The Roles of Post-Translational Modifications on mTOR Signaling.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Amino-acid-induced lysosomal mechanistic target of rapamycin complex 1 (mTORC1) localization through the Rag GTPases is a critical step for its activation by Rheb GTPase. However, how the mTORC1 interacts with Rheb on the lysosome remains elusive. We report that amino acids enhance the polyubiquitination of Rheb (Ub-Rheb), which shows a strong binding preference for mTORC1 and supports its activation, while the Ub-Rheb is subjected to subsequent degradation. Mechanistically, we identified ATXN3 as a Ub-Rheb deubiquitinase whose lysosomal localization is blocked by active Rag heterodimer in response to amino acid stimulation. Consistently, cells lacking functional Rag heterodimer on the lysosome accumulate Ub-Rheb, and blockade of its degradation instigates robust lysosomal mTORC1 localization and its activation without the Ragulator-Rag system. Thus, polyubiquitination of Rheb is an important post-translational modification, which facilitates the binding of mTORC1 to Rheb on the lysosome and is another crosstalk between the amino acid and growth factor signaling for mTORC1 activation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.