ArticleScientific reports2014
Selective small molecule compounds increase BMP-2 responsiveness by inhibiting Smurf1-mediated Smad1/5 degradation.
Article in Scientific reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed.
- TGF-β/BMP signaling in skeletal biology: molecular mechanisms, regulatory networks, and therapeutic implications in development, regeneration, and disease.Bone research · 2026Review
- Article
- The BMP Signaling Pathway: Bridging Maternal-Fetal Crosstalk in Early Pregnancy.Reproductive sciences (Thousand Oaks, Calif.) · 2025Review
- SMURF1: a promising target for colon cancer therapy.Protein & cell · 2025Article
- Increased Kindlin-2 via SMURF1 Inhibition Attenuates Endothelial Permeability and Acute Lung Injury.International journal of molecular sciences · 2025Article
- NEDD4 family E3 ligases in osteoporosis: mechanisms and emerging potential therapeutic targets.Journal of orthopaedic surgery and research · 2025Review
- Expression of SMURF family in pancreatic cancer and its effect on cell proliferation and migration.Frontiers in oncology · 2025Article
- Targeting Smurf1 to block PDK1-Akt signaling in KRAS-mutated colorectal cancer.Nature chemical biology · 2025Article
- Unveiling the Therapeutic Potential of Small Molecule of SVAK-12: A ComprehensiveCurrent medicinal chemistry · 2025Article
- SMURF1/2 Are Novel Regulators of WNK1 Stability.Kinases and phosphatases · 2024Article
- Systematic HOIP interactome profiling reveals critical roles of linear ubiquitination in tissue homeostasis.Nature communications · 2024Article
- Serum Iron Overload Activates the SMAD Pathway and Hepcidin Expression of Hepatocytes via SMURF1.Journal of clinical and translational hepatology · 2024Article
- Smurf1 Modulates Smad Signaling Pathway in Fibrotic Cataract Formation.Investigative ophthalmology & visual science · 2024Article
- Small-Molecule Probes as Pharmacological Tools for the Bone Morphogenetic Protein Signaling Pathway.ACS pharmacology & translational science · 2023Review
- Research Progress in Function and Regulation of E3 Ubiquitin Ligase SMURF1.Current medical science · 2023Review
- Uncovering new insights into the role of the ubiquitin ligase Smurf1 on the regulation of innate immune signaling and resistance to infection.Frontiers in immunology · 2023Review
- TRAF4 Inhibits Bladder Cancer Progression by Promoting BMP/SMAD Signaling.Molecular cancer research : MCR · 2022Article
- Retinoic Acid Receptor Activation Reduces Metastatic Prostate Cancer Bone Lesions by Blocking the Endothelial-to-Osteoblast Transition.Cancer research · 2022Article
- NEDD4 E3 Ligases: Functions and Mechanisms in Bone and Tooth.International journal of molecular sciences · 2022Review
- Discovery of a novel class of benzimidazoles as highly effective agonists of bone morphogenetic protein (BMP) receptor signaling.Scientific reports · 2022Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ubiquitin ligase Smad ubiquitination regulatory factor-1 (Smurf1) negatively regulates bone morphogenetic protein (BMP) pathway by ubiquitinating certain signal components for degradation. Thus, it can be an eligible pharmacological target for increasing BMP signal responsiveness. We established a strategy to discover small molecule compounds that block the WW1 domain of Smurf1 from interacting with Smad1/5 by structure based virtual screening, molecular experimental examination and cytological efficacy evaluation. Our selected hits could reserve the protein level of Smad1/5 from degradation by interrupting Smurf1-Smad1/5 interaction and inhibiting Smurf1 mediated ubiquitination of Smad1/5. Further, these compounds increased BMP-2 signal responsiveness and the expression of certain downstream genes, enhanced the osteoblastic activity of myoblasts and osteoblasts. Our work indicates targeting Smurf1 for inhibition could be an accessible strategy to discover BMP-sensitizers that might be applied in future clinical treatments of bone disorders such as osteopenia.
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