ArticleNature communications2022
An mTORC1-mediated negative feedback loop constrains amino acid-induced FLCN-Rag activation in renal cells with TSC2 loss.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Birt-Hogg-Dubé syndrome.Nature reviews. Disease primers · 2026Review
- Article
- Synergistic role of TFEB/TFE3 and mTORC1 in kidney cystogenesis and tumorigenesis.Cell death and differentiation · 2026Article
- Aggressive high-grade papillary-patterned renal cell carcinomas harboring FLCN mutations: expanding the clinicopathological spectrum in Birt-Hogg-Dubé syndrome and sporadic cases.Virchows Archiv : an international journal of pathology · 2026Article
- Diagnostic utility of novel marker TRIM63 ISH in the workup of uterine perivascular epithelioid cell tumors.Virchows Archiv : an international journal of pathology · 2026Article
- Postoperative management challenges in concurrent endometrioid carcinoma and PEComa a case report.Discover oncology · 2026Article
- FLCN-mutated eosinophilic renal tumors: clinicopathologic and molecular analysis of five cases highlighting morphologic heterogeneity.Virchows Archiv : an international journal of pathology · 2026Article
- Substrate-selective mTORC1 regulation and gene dosage-dependent tissue divergence in Birt-Hogg-Dubé syndrome.Frontiers in oncology · 2026Review
- SFPQ-TFE3 reciprocally regulates mTORC1 and induces lineage plasticity in a mouse model of renal tumorigenesis.Nature communications · 2025Article
- Genetic correlates of malignancy in TFE3-rearranged PEComa: a series of 14 cases.Histopathology · 2025Article
- Coordinated expression of retained introns and poison exons in renal cell carcinoma.Cell reports · 2025Article
- Novel treatment strategies for lymphangioleiomyomatosis: a narrative review.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- The Spectrum of Renal "TFEopathies": Flipping the mTOR Switch in Renal Tumorigenesis.Physiology (Bethesda, Md.) · 2024Review
- Article
- Design and validation of a reporter mouse to study the dynamic regulation of TFEB and TFE3 activity throughAutophagy · 2024Article
- Ragopathies and the rising influence of RagGTPases on human diseases.Nature communications · 2024Review
- O-GlcNAcylation of MITF regulates its activity and CDK4/6 inhibitor resistance in breast cancer.Nature communications · 2024Article
- TFEB drives mTORC1 hyperactivation and kidney disease in Tuberous Sclerosis Complex.Nature communications · 2024Article
- Investigating the role and regulation of GPNMB in progranulin-deficient macrophages.Frontiers in immunology · 2024Article
- The post-translational regulation of transcription factor EB (TFEB) in health and disease.EMBO reports · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
The mechanistic target of rapamycin complex 1 (mTORC1) integrates inputs from growth factors and nutrients, but how mTORC1 autoregulates its activity remains unclear. The MiT/TFE transcription factors are phosphorylated and inactivated by mTORC1 following lysosomal recruitment by RagC/D GTPases in response to amino acid stimulation. We find that starvation-induced lysosomal localization of the RagC/D GAP complex, FLCN:FNIP2, is markedly impaired in a mTORC1-sensitive manner in renal cells with TSC2 loss, resulting in unexpected TFEB hypophosphorylation and activation upon feeding. TFEB phosphorylation in TSC2-null renal cells is partially restored by destabilization of the lysosomal folliculin complex (LFC) induced by FLCN mutants and is fully rescued by forced lysosomal localization of the FLCN:FNIP2 dimer. Our data indicate that a negative feedback loop constrains amino acid-induced, FLCN:FNIP2-mediated RagC activity in renal cells with constitutive mTORC1 signaling, and the resulting MiT/TFE hyperactivation may drive oncogenesis with loss of the TSC2 tumor suppressor.
Indexed as
Identifiers
What OpenQuestion holds
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.