ArticleAutophagy2014
FLCN, a novel autophagy component, interacts with GABARAP and is regulated by ULK1 phosphorylation.
Article in Autophagy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 2 of them syntheses that pooled it.
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Who cites it
53 citing papers in PubMed, 2 syntheses or guidelines pooled it, 79 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).Autophagy · 2016Guideline
- FLCN loss is characterized by SQSTM1/p62 accumulation despite functional autophagy flux in Birt-Hogg-Dubé syndrome-associated kidney cancer.Autophagy reports · 2026Article
- Uncovering the Regulatory Role of Proteins in EBSS-Induced Autophagy Using RNA-Seq Analysis.Biology · 2025Article
- High-throughput behavioural phenotyping of 25 C. elegans disease models including patient-specific mutations.BMC biology · 2025Article
- Comprehensive Physiological and Transcriptomic Profiling of Triploid Pacific Oysters (Biology · 2025Article
- Differential Diagnosis and a Novel Mutation in Birt-Hogg-Dubé Syndrome: Insights from 2 Cases.The American journal of case reports · 2025Article
- Article
- Action and therapeutic targets of folliculin interacting protein 1: a novel signaling mechanism in redox regulation.Frontiers in cell and developmental biology · 2025Review
- Advances in Molecular Mechanisms of Kidney Disease: Integrating Renal Tumorigenesis of Hereditary Cancer Syndrome.International journal of molecular sciences · 2024Review
- Characterizing the tumor suppressor activity of FLCN in Birt-Hogg-Dubé syndrome through transcriptiomic and proteomic analysis.Research square · 2024Article
- Proteomics Analysis of Pregnancy in Ewes under Heat Stress Conditions and Melatonin Administration.Animals : an open access journal from MDPI · 2024Article
- Tuberous Sclerosis Complex cell-derived EVs have an altered protein cargo capable of regulating their microenvironment and have potential as disease biomarkers.Journal of extracellular vesicles · 2023Article
- Review
- Autophagy induction promoted by mNature communications · 2022Article
- Autophagy and beyond: Unraveling the complexity of UNC-51-like kinase 1 (ULK1) from biological functions to therapeutic implications.Acta pharmaceutica Sinica. B · 2022Review
- Mechanisms in Graves Eye Disease: Apoptosis as the End Point of Insulin-Like Growth Factor 1 Receptor Inhibition.Thyroid : official journal of the American Thyroid Association · 2022Article
- Human Umbilical Cord Blood Mononuclear Cells Ameliorate CClFrontiers in pharmacology · 2022Article
- GABARAP sequesters the FLCN-FNIP tumor suppressor complex to couple autophagy with lysosomal biogenesis.Science advances · 2021Article
- Molecular Pathogenesis and Immune Evasion of Vesicular Stomatitis New Jersey Virus Inferred from Genes Expression Changes in Infected Porcine Macrophages.Pathogens (Basel, Switzerland) · 2021Article
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 9 countries.
Funding
Abstract
Birt-Hogg-Dubé (BHD) syndrome is a rare autosomal dominant condition caused by mutations in the FLCN gene and characterized by benign hair follicle tumors, pneumothorax, and renal cancer. Folliculin (FLCN), the protein product of the FLCN gene, is a poorly characterized tumor suppressor protein, currently linked to multiple cellular pathways. Autophagy maintains cellular homeostasis by removing damaged organelles and macromolecules. Although the autophagy kinase ULK1 drives autophagy, the underlying mechanisms are still being unraveled and few ULK1 substrates have been identified to date. Here, we identify that loss of FLCN moderately impairs basal autophagic flux, while re-expression of FLCN rescues autophagy. We reveal that the FLCN complex is regulated by ULK1 and elucidate 3 novel phosphorylation sites (Ser406, Ser537, and Ser542) within FLCN, which are induced by ULK1 overexpression. In addition, our findings demonstrate that FLCN interacts with a second integral component of the autophagy machinery, GABA(A) receptor-associated protein (GABARAP). The FLCN-GABARAP association is modulated by the presence of either folliculin-interacting protein (FNIP)-1 or FNIP2 and further regulated by ULK1. As observed by elevation of GABARAP, sequestome 1 (SQSTM1) and microtubule-associated protein 1 light chain 3 (MAP1LC3B) in chromophobe and clear cell tumors from a BHD patient, we found that autophagy is impaired in BHD-associated renal tumors. Consequently, this work reveals a novel facet of autophagy regulation by ULK1 and substantially contributes to our understanding of FLCN function by linking it directly to autophagy through GABARAP and ULK1.
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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.