ArticleThe Journal of biological chemistry2016
Smad7 Protein Interacts with Receptor-regulated Smads (R-Smads) to Inhibit Transforming Growth Factor-β (TGF-β)/Smad Signaling.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers.
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Who cites it
110 citing papers in PubMed, 185 citations in OpenAlex.
- HnRNPA2B1 tunes antimycobacterial immune responses in macrophages through alternative splicing ofInfection and immunity · 2026Article
- Aging and cancer: current understandings and future perspectives.Signal transduction and targeted therapy · 2026Review
- Molecular mechanisms and multi-organ regulatory roles of anti-Müllerian hormone in female reproduction.Communications biology · 2026Review
- Transcriptomic Profiling Identifies Potential Prognostic Genes in Vietnamese Patients with Non-Small-Cell Lung Cancer.Current issues in molecular biology · 2026Article
- Tissue-specific I-Smad mechanisms revealed by structure-function analysis inLife science alliance · 2026Article
- The Ubiquitin-Specific Protease Family: Master Regulators of Renal Fibrosis Pathogenesis and Therapeutic Targets.International journal of molecular sciences · 2026Review
- IFN-γ and TNF-α Impair Lung Development by Upregulating SMAD7 to Inhibit TGF-β Signaling Pathway and ECM Dysregulation.Inflammation · 2026Article
- Uncoupling Metastasis and Epithelial-to-Mesenchymal Transition in sgP19/kRAS-Driven Spontaneous Metastatic Liver Tumor Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Macrophage NEDD4L restrains liver fibrosis by preventing scar-associated macrophage expansion via ubiquitination of phospho-SMAD3.International journal of biological sciences · 2026Article
- Coenzyme Q10 alleviates silicotic fibrosis in rats through the TGF-β1/Smad pathway.Frontiers in pharmacology · 2026Article
- Cardiomyocyte-derived BDNF restricts cardiac fibrosis by decreasing the activity of the TGF-β/Smad2/3 pathway and increasing Smad7 expression.Frontiers in cell and developmental biology · 2026Article
- HnRNPA2B1 tunes antimycobacterial immune responses in macrophages through alternative splicing ofbioRxiv : the preprint server for biology · 2025Article
- Role of Growth Factors in the Pathogenesis of Systemic-Sclerosis-Associated Fibrosis.International journal of molecular sciences · 2025Review
- Propolis compound inhibits profibrotic TGF-β1/SMAD signalling in human fibroblasts.Scientific reports · 2025Article
- A TFEB-TGFβ axis systemically regulates diapause, stem cell resilience and protects against a senescence-like state.Nature aging · 2025Article
- OTUD3 inhibits breast cancer cell metastasis by regulating TGF-β pathway through deubiquitinating SMAD7.Cancer cell international · 2025Article
- Determination of both the expression and serum levels of epidermal growth factor and transforming growth factor β1 genes in COVID-19.Scientific reports · 2025Article
- A Golden Shield: The Protective Role of Curcumin against Liver Fibrosis.Current medicinal chemistry · 2025Review
- Therapeutic potential of traditional Chinese medicine in pancreatic fibrosis: mechanisms of TCM formulas and active ingredients.Frontiers in pharmacology · 2025Review
- Unraveling the Role of N6-Methylation Modification: From Bone Biology to Osteoporosis.International journal of medical sciences · 2025Review
50 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TGF-β is a pleiotropic cytokine that regulates a wide range of cellular actions and pathophysiological processes. TGF-β signaling is spatiotemporally fine-tuned. As a key negative regulator of TGF-β signaling, Smad7 exerts its inhibitory effects by blocking receptor activity, inducing receptor degradation or interfering with Smad-DNA binding. However, the functions and the molecular mechanisms underlying the actions of Smad7 in TGF-β signaling are still not fully understood. In this study we report a novel mechanism whereby Smad7 antagonizes TGF-β signaling at the Smad level. Smad7 oligomerized with R-Smad proteins upon TGF-β signaling and directly inhibited R-Smad activity, as assessed by Gal4-luciferase reporter assays. Mechanistically, Smad7 competes with Smad4 to associate with R-Smads and recruits the E3 ubiquitin ligase NEDD4L to activated R-Smads, leading to their polyubiquitination and proteasomal degradation. Similar to the R-Smad-Smad4 oligomerization, the interaction between R-Smads and Smad7 is mediated by their mad homology 2 (MH2) domains. A positive-charged basic region including the L3/β8 loop-strand module and adjacent amino acids in the MH2 domain of Smad7 is essential for the interaction. These results shed new light on the regulation of TGF-β signaling by Smad7.
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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.