ArticleThe Journal of cell biology2020
EGF receptor-mediated FUS phosphorylation promotes its nuclear translocation and fibrotic signaling.
Article in The Journal of cell biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- Article
- Emerging role of FUS in TGFB1 and COL1A1 transcription dependent on GADD45B to induce NASH-fibrosis.Journal of molecular cell biology · 2026Article
- Integrated bioinformatic analysis of biomarkers, pathways, and immune cell infiltration in ossification of the ligamentum flavum.International journal of clinical and experimental pathology · 2026Article
- The epidermal growth factor receptor regulates YAP signalling and promotes diabetic retinal fibrosis by modulating the degradation of SAV1.Journal of translational medicine · 2025Article
- Integrins in the kidney - beyond the matrix.Nature reviews. Nephrology · 2025Review
- Review
- The peptide genomic therapy increases antibacterial immunity and survival in sepsis by reprograming the gene orthologs of human immunodeficiencies in the spleen and lungs.Frontiers in immunology · 2025Article
- Regulation of HNRNP family by post-translational modifications in cancer.Cell death discovery · 2024Review
- Advances and transgressions of nuclear transport checkpoint inhibitors.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Cytoplasmic retention of the DNA/RNA-binding protein FUS ameliorates organ fibrosis in mice.The Journal of clinical investigation · 2024Article
- Novel KMT2B gene mutation in MUC4 positive low-grade fibromyxoid sarcoma.Diagnostic pathology · 2024Article
- Article
- Decrypting Integrins by Mixed-Solvent Molecular Dynamics Simulations.Journal of chemical information and modeling · 2023Article
- Activation of thousands of genes in the lungs and kidneys by sepsis is countered by the selective nuclear blockade.Frontiers in immunology · 2023Article
- Regulation of Podocyte Injury by CircHIPK3/FUS Complex in Diabetic Kidney Disease.International journal of biological sciences · 2022Article
- Hyperlipidemic hypersensitivity to lethal microbial inflammation and its reversal by selective targeting of nuclear transport shuttles.Scientific reports · 2021Article
- The Vanderbilt O'Brien Kidney Center.American journal of physiology. Renal physiology · 2021Review
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
Excessive accumulation of collagen leads to fibrosis. Integrin α1β1 (Itgα1β1) prevents kidney fibrosis by reducing collagen production through inhibition of the EGF receptor (EGFR) that phosphorylates cytoplasmic and nuclear proteins. To elucidate how the Itgα1β1/EGFR axis controls collagen synthesis, we analyzed the levels of nuclear tyrosine phosphorylated proteins in WT and Itgα1-null kidney cells. We show that the phosphorylation of the RNA-DNA binding protein fused in sarcoma (FUS) is higher in Itgα1-null cells. FUS contains EGFR-targeted phosphorylation sites and, in Itgα1-null cells, activated EGFR promotes FUS phosphorylation and nuclear translocation. Nuclear FUS binds to the collagen IV promoter, commencing gene transcription that is reduced by inhibiting EGFR, down-regulating FUS, or expressing FUS mutated in the EGFR-targeted phosphorylation sites. Finally, a cell-penetrating peptide that inhibits FUS nuclear translocation reduces FUS nuclear content and collagen IV transcription. Thus, EGFR-mediated FUS phosphorylation regulates FUS nuclear translocation and transcription of a major profibrotic collagen gene. Targeting FUS nuclear translocation offers a new antifibrotic therapy.
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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.