ArticleGenes & development2008
Axin and GSK3- control Smad3 protein stability and modulate TGF- signaling.
Article in Genes & development, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 148 papers.
What it found
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Who cites it
148 citing papers in PubMed, 250 citations in OpenAlex.
- Dual Inhibition of GSK3 and JAK by BIO Suppresses Osteoblast Differentiation and Mineralization of Human Mesenchymal Cells.Current issues in molecular biology · 2026Article
- Inhibition of TGF-beta signaling protects from alpha-synuclein induced toxicity.Cell death discovery · 2025Article
- Inhibition of Wnt signaling in primary human hepatocytes promotes Plasmodium falciparum liver stage development.PLoS pathogens · 2025Article
- Downregulation of miR-27a-3p Modulates TGF-β Signaling and Dysregulates Metabolism in Glioblastoma.International journal of molecular sciences · 2025Article
- Glycogen synthase kinase 3β: a key player in progressive chronic kidney disease.Clinical science (London, England : 1979) · 2025Review
- Exploring the Antifibrotic Mechanisms of Ghrelin: Modulating TGF-β Signalling in Organ Fibrosis.Expert reviews in molecular medicine · 2024Review
- Apoptotic vesicles rescue impaired mesenchymal stem cells and their therapeutic capacity for osteoporosis by restoring miR-145a-5p deficiency.Journal of nanobiotechnology · 2024Article
- Apoptotic vesicles rescue impaired mesenchymal stem cells and their therapeutic capacity for osteoporosis by restoring miR-145a-5p deficiency.Research square · 2024Article
- TGF-β signaling in health, disease, and therapeutics.Signal transduction and targeted therapy · 2024Review
- MicroRNAs regulating signaling pathways in cardiac fibrosis: potential role of the exercise training.American journal of physiology. Heart and circulatory physiology · 2024Review
- Targeting SMAD-Dependent Signaling: Considerations in Epithelial and Mesenchymal Solid Tumors.Pharmaceuticals (Basel, Switzerland) · 2024Review
- The scaffold protein AXIN1: gene ontology, signal network, and physiological function.Cell communication and signaling : CCS · 2024Review
- Application of dental pulp stem cells for bone regeneration.Frontiers in medicine · 2024Review
- The impact of canonical Wnt transcriptional repressors TLE3 and TLE4 on postsynaptic transcription at the neuromuscular junction.Frontiers in molecular neuroscience · 2024Article
- Off-Target Effects of P2Y12 Receptor Inhibitors: Focus on Early Myocardial Fibrosis Modulation.International journal of molecular sciences · 2023Review
- Targeting transforming growth factor beta signaling in metastatic osteosarcoma.Journal of bone oncology · 2023Review
- PMCells · 2023Article
- GSK-3 at the heart of cardiometabolic diseases: Isoform-specific targeting is critical to therapeutic benefit.Biochimica et biophysica acta. Molecular basis of disease · 2023Review
- Chicken Glycogen Synthase Kinase 3β Suppresses Innate Immune Responses and Enhances Avian Leukosis Virus Replication in DF-1 Cells.Microbiology spectrum · 2023Article
- Adriamycin induces cardiac fibrosis in mice via PRMT5-mediated cardiac fibroblast activation.Acta pharmacologica Sinica · 2023Article
88 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The broad range of biological responses elicited by transforming growth factor-beta (TGF-beta) in various types of tissues and cells is mainly determined by the expression level and activity of the effector proteins Smad2 and Smad3. It is not fully understood how the baseline properties of Smad3 are regulated, although this molecule is in complex with many other proteins at the steady state. Here we show that nonactivated Smad3, but not Smad2, undergoes proteasome-dependent degradation due to the concerted action of the scaffolding protein Axin and its associated kinase, glycogen synthase kinase 3-beta (GSK3-beta). Smad3 physically interacts with Axin and GSK3-beta only in the absence of TGF-beta. Reduction in the expression or activity of Axin/GSK3-beta leads to increased Smad3 stability and transcriptional activity without affecting TGF-beta receptors or Smad2, whereas overexpression of these proteins promotes Smad3 basal degradation and desensitizes cells to TGF-beta. Mechanistically, Axin facilitates GSK3-beta-mediated phosphorylation of Smad3 at Thr66, which triggers Smad3 ubiquitination and degradation. Thr66 mutants of Smad3 show altered protein stability and hence transcriptional activity. These results indicate that the steady-state stability of Smad3 is an important determinant of cellular sensitivity to TGF-beta, and suggest a new function of the Axin/GSK3-beta complex in modulating critical TGF-beta/Smad3-regulated processes during development and tumor progression.
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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.