ArticleMolecular cell2023
Ring domains are essential for GATOR2-dependent mTORC1 activation.
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 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- GATOR2 regulates the nutrient-dependent recruitment of GATOR1 to lysosomes.bioRxiv : the preprint server for biology · 2026Article
- Integrated pan cancer analysis with breast cancer validation identifies SEC13 homolog as prognostic biomarker and immunotherapy target.Scientific reports · 2026Article
- Structure and function of the yeast amino acid-sensing SEAC-EGOC supercomplex.Nature structural & molecular biology · 2026Article
- Mechanisms of mTORC1 and GCN2 amino acid sensing pathways in tumorigenesis and metastatic progression (Review).International journal of molecular medicine · 2026Review
- mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics.Signal transduction and targeted therapy · 2025Review
- IFN-γ-driven UBE2D3 upregulation impairs antigen presentation pathways and anti-tumor immunity in pancreatic cancer.Nature communications · 2025Article
- Article
- The Molecular Basis of Amino Acids Sensing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Survival strategies of cancer cells: the role of macropinocytosis in nutrient acquisition, metabolic reprogramming, and therapeutic targeting.Autophagy · 2025Review
- Article
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- Increased translation driven by non-canonical EZH2 creates a synthetic vulnerability in enzalutamide-resistant prostate cancer.Nature communications · 2024Article
- Review
- Histone H2B lysine 122 and lysine 130, as the putative targets of Penicillium oxalicum LaeA, play important roles in asexual development, expression of secondary metabolite gene clusters, and extracellular glycoside hydrolase synthesis.World journal of microbiology & biotechnology · 2024Article
- New insights into GATOR2-dependent interactions and its conformational changes in amino acid sensing.Bioscience reports · 2024Article
- The GATOR2 complex maintains lysosomal-autophagic function by inhibiting the protein degradation of MiT/TFEs.Molecular cell · 2024Article
- Structures and Functions of the Human GATOR1 Complex.Sub-cellular biochemistry · 2024Review
- The molecular basis of nutrient sensing and signalling by mTORC1 in metabolism regulation and disease.Nature reviews. Molecular cell biology · 2023Review
- Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease.Signal transduction and targeted therapy · 2023Review
- GATOR2 rings GATOR1 to speak to mTORC1.Molecular cell · 2023Article
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Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
Abstract
The GATOR2-GATOR1 signaling axis is essential for amino-acid-dependent mTORC1 activation. However, the molecular function of the GATOR2 complex remains unknown. Here, we report that disruption of the Ring domains of Mios, WDR24, or WDR59 completely impedes amino-acid-mediated mTORC1 activation. Mechanistically, via interacting with Ring domains of WDR59 and WDR24, the Ring domain of Mios acts as a hub to maintain GATOR2 integrity, disruption of which leads to self-ubiquitination of WDR24. Physiologically, leucine stimulation dissociates Sestrin2 from the Ring domain of WDR24 and confers its availability to UBE2D3 and subsequent ubiquitination of NPRL2, contributing to GATOR2-mediated GATOR1 inactivation. As such, WDR24 ablation or Ring deletion prevents mTORC1 activation, leading to severe growth defects and embryonic lethality at E10.5 in mice. Hence, our findings demonstrate that Ring domains are essential for GATOR2 to transmit amino acid availability to mTORC1 and further reveal the essentiality of nutrient sensing during embryonic development.
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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.