ArticleThe Journal of cell biology2018
GATOR1-dependent recruitment of FLCN-FNIP to lysosomes coordinates Rag GTPase heterodimer nucleotide status in response to amino acids.
Article in The Journal of cell biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 72 citations in OpenAlex.
- Renal cell carcinoma: molecular understanding and therapeutic development.Cell death and differentiation · 2026Review
- Lysosome heterogeneity and diversity mapped through its distinct cellular functions.Cellular and molecular life sciences : CMLS · 2025Review
- Eukaryote-Wide Distribution of a Family of Longin Domain-Containing GAP Complexes for Small GTPases.Traffic (Copenhagen, Denmark) · 2025Article
- Article
- A novel uORF regulates folliculin to promote cell growth and lysosomal biogenesis during cardiac stress.Scientific reports · 2025Article
- Action and therapeutic targets of folliculin interacting protein 1: a novel signaling mechanism in redox regulation.Frontiers in cell and developmental biology · 2025Review
- Reactive oxygen species control protein degradation at the mitochondrial import gate.Molecular cell · 2024Article
- The Spectrum of Renal "TFEopathies": Flipping the mTOR Switch in Renal Tumorigenesis.Physiology (Bethesda, Md.) · 2024Review
- FNIP1 suppresses colorectal cancer progression through inhibiting STAT3 phosphorylation and nuclear translocation.iScience · 2024Article
- Lysosomal TBK1 responds to amino acid availability to relieve Rab7-dependent mTORC1 inhibition.The EMBO journal · 2024Article
- Ragopathies and the rising influence of RagGTPases on human diseases.Nature communications · 2024Review
- Characterizing the tumor suppressor activity of FLCN in Birt-Hogg-Dubé syndrome through transcriptiomic and proteomic analysis.Research square · 2024Article
- Stress-induced microautophagy is coordinated with lysosome biogenesis and regulated by PIKfyve.Molecular biology of the cell · 2024Article
- Lysosomal TBK1 Responds to Amino Acid Availability to Relieve Rab7-Dependent mTORC1 Inhibition.bioRxiv : the preprint server for biology · 2023Article
- The post-translational regulation of transcription factor EB (TFEB) in health and disease.EMBO reports · 2023Review
- Targeting the biology of aging with mTOR inhibitors.Nature aging · 2023Review
- The KEAP1-NRF2 pathway regulates TFEB/TFE3-dependent lysosomal biogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Regulation of mTORC1 by the Rag GTPases.Biochemical Society transactions · 2023Review
- Brain-enriched RagB isoforms regulate the dynamics of mTORC1 activity through GATOR1 inhibition.Nature cell biology · 2022Article
- Emerging Link between Tsc1 and FNIP Co-Chaperones of Hsp90 and Cancer.Biomolecules · 2022Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Folliculin (FLCN) is a tumor suppressor that coordinates cellular responses to changes in amino acid availability via regulation of the Rag guanosine triphosphatases. FLCN is recruited to lysosomes during amino acid starvation, where it interacts with RagA/B as a heterodimeric complex with FLCN-interacting proteins (FNIPs). The FLCN-FNIP heterodimer also has GTPase-activating protein (GAP) activity toward RagC/D. These properties raised two important questions. First, how is amino acid availability sensed to regulate lysosomal abundance of FLCN? Second, what is the relationship between FLCN lysosome localization, RagA/B interactions, and RagC/D GAP activity? In this study, we show that RagA/B nucleotide status determines the FLCN-FNIP1 recruitment to lysosomes. Starvation-induced FLCN-FNIP lysosome localization requires GAP activity toward Rags 1 (GATOR1), the GAP that converts RagA/B to the guanosine diphosphate (GDP)-bound state. This places FLCN-FNIP recruitment to lysosomes under the control of amino acid sensors that act upstream of GATOR1. By binding to RagA/B
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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.