ArticleCell research2019
Ubiquitination of Rheb governs growth factor-induced mTORC1 activation.
Article in Cell research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 132 citations in OpenAlex.
- MAPA: A Semantic Network Framework for Functional Module Discovery and Interpretation in Multi-Omics Data.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The FAM234A-USP4 axis governs T-cell fate through the dual regulation of mTOR and RORγt.Cellular & molecular immunology · 2026Article
- RagC senses β-hydroxybutyrate abundancy to suppress mTORC1.Protein & cell · 2026Article
- FAM234A acts as a switch between Th17 and Treg cell fate decisions that control inflammatory bowel disease.Cellular & molecular immunology · 2026Article
- Sirtuin 2 inhibits global protein synthesis via Rheb-GTPase degradation.EMBO reports · 2026Article
- Ubiquitination modifications as central regulators of metabolic dysfunction in type 2 diabetes mellitus.Frontiers in endocrinology · 2026Review
- Mechanisms of mTORC1 and GCN2 amino acid sensing pathways in tumorigenesis and metastatic progression (Review).International journal of molecular medicine · 2026Review
- Article
- Branched-chain amino acids in muscle growth: mechanisms, physiological functions, and applications.Journal of animal science and biotechnology · 2025Review
- Prefrontal oxytocin receptor positive cells mediate stress-induced anxiety in tuberous sclerosis complex.Communications biology · 2025Article
- Muscle Insulin Resistance Elicits Muscle Atrophy in Obesity.Current obesity reports · 2025Review
- The Role of the PI3K/Akt/mTOR Pathway in Atherosclerosis: Mechanisms, Therapeutic Potential, and Emerging Targeted Treatments.Current atherosclerosis reports · 2025Review
- HUWE1 stimulates mTORC1 activity by enhancing Rheb interaction with mTORC1 and supports de novo pyrimidine synthesis.Cell reports · 2025Article
- AKT and DUBs: a bidirectional relationship.Cellular & molecular biology letters · 2025Review
- Lysosomal quality control Review.Autophagy · 2025Review
- Lysosomal EGFR acts as a Rheb-GEF independent of its kinase activity to activate mTORC1.Cell research · 2025Article
- Role of the USP family in autophagy regulation and cancer progression.Apoptosis : an international journal on programmed cell death · 2025Review
- RAB3B Dictates mTORC1/S6 Signaling in Chordoma and Predicts Response to mTORC1-Targeted Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Identification of autophagy-related immune targets for enhancing immunotherapy in pancreatic cancer aggressiveness.Discover oncology · 2025Article
- Targeting intracellular autophagic process for the treatment of post-stroke ischemia/reperfusion injury.Animal models and experimental medicine · 2025Review
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mechanistic target of rapamycin mTOR complex 1 (mTORC1) plays a key role in the integration of various environmental signals to regulate cell growth and metabolism. mTORC1 is recruited to the lysosome where it is activated by its interaction with GTP-bound Rheb GTPase. However, the regulatory mechanism of Rheb activity remains largely unknown. Here, we show that ubiquitination governs the nucleotide-bound status of Rheb. Lysosome-anchored E3 ligase RNF152 catalyzes Rheb ubiquitination and promotes its binding to the TSC complex. EGF enhances the deubiquitination of Rheb through AKT-dependent USP4 phosphorylation, leading to the release of Rheb from the TSC complex. Functionally, ubiquitination of Rheb is linked to mTORC1-mediated signaling and consequently regulates tumor growth. Thus, we propose a mechanistic model whereby Rheb-mediated mTORC1 activation is dictated by a dynamic opposing act between Rheb ubiquitination and deubiquitination that are catalyzed by RNF152 and USP4 respectively.
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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.