ArticleThe Journal of cell biology2022
pVHL-mediated SMAD3 degradation suppresses TGF-β signaling.
Article in The Journal of cell biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Understanding the role of hypoxia inducible factors in liver fibrosis and future therapeutic applications.iLIVER · 2026Review
- Cystathionine γ-Lyase-Dependent S-Sulfhydration of Smad3: A Novel Target to Alleviate Fibrosis in Systemic Sclerosis.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Senescent BMSC-Derived Thbs1 Drives Inflammaging and Impairs Bone Regeneration by Suppressing PINK1/Parkin-Mediated Mitophagy in Macrophages.Aging cell · 2026Article
- Bioinformatics Identification and Molecular Docking Validation of Post-Translational Modification-Related Hub Genes as Diagnostic Biomarkers and Therapeutic Targets in Myocardial Fibrosis.International journal of molecular sciences · 2026Article
- Von Hippel-Lindau/Hypoxia Inducible Factor Axis in Glioblastoma.International journal of molecular sciences · 2025Review
- pVHL regulates protein stability of the TCF/LEF transcription factor family via ubiquitin-independent proteasomal degradation.Cellular and molecular life sciences : CMLS · 2025Article
- Ang-1 and VEGF: central regulators of angiogenesis.Molecular and cellular biochemistry · 2025Review
- Linc00673-V3 positively regulates autophagy by promoting Smad3-mediatedLife science alliance · 2024Article
- Druggable Biomarkers Altered in Clear Cell Renal Cell Carcinoma: Strategy for the Development of Mechanism-Based Combination Therapy.International journal of molecular sciences · 2023Review
- Generation of nanoscopic membrane curvature for membrane trafficking.Nature reviews. Molecular cell biology · 2023Review
- Irradiation induces DJ-1 secretion from esophageal squamous cell carcinoma cells to accelerate metastasis of bystander cells via a TGF-β1 positive feedback loop.Journal of experimental & clinical cancer research : CR · 2022Article
- Review
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transforming growth factor β (TGF-β) signaling plays a fundamental role in metazoan development and tissue homeostasis. However, the molecular mechanisms concerning the ubiquitin-related dynamic regulation of TGF-β signaling are not thoroughly understood. Using a combination of proteomics and an siRNA screen, we identify pVHL as an E3 ligase for SMAD3 ubiquitination. We show that pVHL directly interacts with conserved lysine and proline residues in the MH2 domain of SMAD3, triggering degradation. As a result, the level of pVHL expression negatively correlates with the expression and activity of SMAD3 in cells, Drosophila wing, and patient tissues. In Drosophila, loss of pVHL leads to the up-regulation of TGF-β targets visible in a downward wing blade phenotype, which is rescued by inhibition of SMAD activity. Drosophila pVHL expression exhibited ectopic veinlets and reduced wing growth in a similar manner as upon loss of TGF-β/SMAD signaling. Thus, our study demonstrates a conserved role of pVHL in the regulation of TGF-β/SMAD3 signaling in human cells and Drosophila wing development.
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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.