ArticleNature communications2024
USF2 and TFEB compete in regulating lysosomal and autophagy genes.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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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.
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Who cites it
16 citing papers in PubMed.
- USF2-Mediated APOE-Cholesterol Signaling Promotes CTC Clustering and Metastasis in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2026Article
- The impactful role of the HDACs in the regulation of gene expression and as targets for disease therapy.Science advances · 2026Review
- Transcriptional and epigenetic regulation of autophagy: mechanisms, disease relevance and therapeutic opportunities.Signal transduction and targeted therapy · 2026Review
- Mitophagy and Ubiquitination Coordinate Context-Specific Mitochondrial Quality Control and EMT/MET Plasticity to Drive Cancer Cell Invasion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- CTGF knockdown in Vero cells reduces autophagy and adhesion and promotes short-term suspension adaptation.Frontiers in bioengineering and biotechnology · 2026Article
- Lysosomal membrane homeostasis and its importance in physiology and disease.Nature reviews. Molecular cell biology · 2026Review
- Association of thymoquinone-induced changes in PINK1, DRP1, TFEB, and cytochrome c expression with mitochondrial dynamics and apoptosis in HepG2 and HDF cells.Medical oncology (Northwood, London, England) · 2025Article
- Dual mechanism of autophagy gene repression by PHF23 and therapeutic potential of its inhibition in protein aggregation disorders.Nucleic acids research · 2025Article
- Blueprint of Collapse: Precision Biomarkers, Molecular Cascades, and the Engineered Decline of Fast-Progressing ALS.International journal of molecular sciences · 2025Review
- Decoding the dual role of autophagy in cancer through transcriptional and epigenetic regulation.FEBS letters · 2025Review
- Identification and experimental validation of ulcerative colitis-associated hub genes through integrated WGCNA and lysosomal autophagy analysis.Human genomics · 2025Article
- Inflammation-induced lysosomal dysfunction in human iPSC-derived microglia is exacerbated by APOE 4/4 genotype.Journal of neuroinflammation · 2025Article
- Transcriptional repression of autophagy and lysosome biogenesis.Autophagy · 2025Article
- STING mediates lysosomal quality control and recovery through its proton channel function and TFEB activation in lysosomal storage disorders.Molecular cell · 2025Article
- Dysregulation of autophagy during photoaging reduce oxidative stress and inflammatory damage caused by UV.Frontiers in pharmacology · 2025Review
- Epigenetic dysregulation-induced metabolic reprogramming fuels tumor progression in bladder cancer.Frontiers in molecular biosciences · 2025Article
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
Autophagy, a highly conserved self-digestion process crucial for cellular homeostasis, is triggered by various environmental signals, including nutrient scarcity. The regulation of lysosomal and autophagy-related processes is pivotal to maintaining cellular homeostasis and basal metabolism. The consequences of disrupting or diminishing lysosomal and autophagy systems have been investigated; however, information on the implications of hyperactivating lysosomal and autophagy genes on homeostasis is limited. Here, we present a mechanism of transcriptional repression involving upstream stimulatory factor 2 (USF2), which inhibits lysosomal and autophagy genes under nutrient-rich conditions. We find that USF2, together with HDAC1, binds to the CLEAR motif within lysosomal genes, thereby diminishing histone H3K27 acetylation, restricting chromatin accessibility, and downregulating lysosomal gene expression. Under starvation, USF2 competes with transcription factor EB (TFEB), a master transcriptional activator of lysosomal and autophagy genes, to bind to target gene promoters in a phosphorylation-dependent manner. The GSK3β-mediated phosphorylation of the USF2 S155 site governs USF2 DNA-binding activity, which is involved in lysosomal gene repression. These findings have potential applications in the treatment of protein aggregation-associated diseases, including α1-antitrypsin deficiency. Notably, USF2 repression is a promising therapeutic strategy for lysosomal and autophagy-related diseases.
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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 Socratic graph.