ArticleScience (New York, N.Y.)2013
A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1.
Article in Science (New York, N.Y.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 657 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
657 citing papers in PubMed, 0 citations in OpenAlex.
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- Synergistic role of TFEB/TFE3 and mTORC1 in kidney cystogenesis and tumorigenesis.Cell death and differentiation · 2026Article
- SLC4A7/NBCn1 maintains intracellular pH to support mTORC1 activity and antibody-secreting cell differentiation.Nature communications · 2026Article
- Muscular dystrophy-associated lamin variants disrupt cellular organization through a nucleolar-ribosomal axis.Science advances · 2026Article
- GATOR1 signaling defects promote astrocytic metabolic rewiring and excitatory neurotransmitter cycling.EMBO reports · 2026Article
- Translational resistance to amino acid starvation in breast cancer cells revealed by ribosome profiling.iScience · 2026Article
- Conserved Transcriptomic Signatures of Sirt6 Activity: A Cross-Species RNA-seq Meta-analysis.bioRxiv : the preprint server for biology · 2026Article
- GATOR2 regulates the nutrient-dependent recruitment of GATOR1 to lysosomes.bioRxiv : the preprint server for biology · 2026Article
- Article
- Amino-acids-mTORC1-driven DDA1 phosphorylation promotes DNA repair and glioblastoma progression.Cell communication and signaling : CCS · 2026Article
- Clinical and Genetic Characterization of Inherited NPRL3 Splice Variants in Two Patients With Epilepsy.Molecular genetics & genomic medicine · 2026Article
- The Legionella pneumophila type IVb secretion system effector BinA subverts amino acid transport to sensitize TORC1 signaling in macrophages.PLoS pathogens · 2026Article
- Inflammation starves antitumour immunity.Nature cell biology · 2026Article
- Aberrant amino acid-sensing promotes immunotherapy resistance via the inflammatory cytokine-ZBTB5-mTORC1 axis.Nature cell biology · 2026Article
- Integrative In Silico mRNA-miRNA Profiling of mTOR Pathway Dysregulation in High-Grade Serous Ovarian Carcinoma.Cancers · 2026Article
- Structure and function of the yeast amino acid-sensing SEAC-EGOC supercomplex.Nature structural & molecular biology · 2026Article
- Lysosomal phosphoinositide turnover acts upstream of RagGTPase-mTORC1 and controls muscle growth.Nature metabolism · 2026Article
597 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 7 institutions in 1 country.
Funding
Abstract
The mTOR complex 1 (mTORC1) pathway promotes cell growth in response to many cues, including amino acids, which act through the Rag guanosine triphosphatases (GTPases) to promote mTORC1 translocation to the lysosomal surface, its site of activation. Although progress has been made in identifying positive regulators of the Rags, it is unknown if negative factors also exist. Here, we identify GATOR as a complex that interacts with the Rags and is composed of two subcomplexes we call GATOR1 and -2. Inhibition of GATOR1 subunits (DEPDC5, Nprl2, and Nprl3) makes mTORC1 signaling resistant to amino acid deprivation. In contrast, inhibition of GATOR2 subunits (Mios, WDR24, WDR59, Seh1L, and Sec13) suppresses mTORC1 signaling, and epistasis analysis shows that GATOR2 negatively regulates DEPDC5. GATOR1 has GTPase-activating protein (GAP) activity for RagA and RagB, and its components are mutated in human cancer. In cancer cells with inactivating mutations in GATOR1, mTORC1 is hyperactive and insensitive to amino acid starvation, and such cells are hypersensitive to rapamycin, an mTORC1 inhibitor. Thus, we identify a key negative regulator of the Rag GTPases and reveal that, like other mTORC1 regulators, Rag function can be deregulated in cancer.
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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.