ArticleNucleic acids research2008
SMAD3 prevents binding of NKX2.1 and FOXA1 to the SpB promoter through its MH1 and MH2 domains.
Article in Nucleic acids research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
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- Mast4 determines the cell fate of MSCs for bone and cartilage development.Nature communications · 2022Article
- TGF-β Signaling in Lung Health and Disease.International journal of molecular sciences · 2018Review
- Intracellular and extracellular TGF-β signaling in cancer: some recent topics.Frontiers of medicine · 2018Review
- TGF beta inhibits expression of SP-A, SP-B, SP-C, but not SP-D in human alveolar type II cells.Biochemical and biophysical research communications · 2018Article
- A Role for the Transcription Factor Nk2 Homeobox 1 in Schizophrenia: Convergent Evidence from Animal and Human Studies.Frontiers in behavioral neuroscience · 2016Article
- The miR-200 family and its targets regulate type II cell differentiation in human fetal lung.The Journal of biological chemistry · 2015Article
- Nuclear mobility and activity of FOXA1 with androgen receptor are regulated by SUMOylation.Molecular endocrinology (Baltimore, Md.) · 2014Article
- A Smad3 and TTF-1/NKX2-1 complex regulates Smad4-independent gene expression.Cell research · 2014Article
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- Tumor-promoting functions of transforming growth factor-β in progression of cancer.Upsala journal of medical sciences · 2012Review
- MiR-365 regulates lung cancer and developmental gene thyroid transcription factor 1.Cell cycle (Georgetown, Tex.) · 2012Article
- JUN-CCAAT/enhancer-binding protein complexes inhibit surfactant-associated protein B promoter activity.American journal of respiratory cell and molecular biology · 2011Article
- Article
- TGFbeta signalling: a complex web in cancer progression.Nature reviews. Cancer · 2010Review
- Foxa1 functions as a pioneer transcription factor at transposable elements to activate Afp during differentiation of embryonic stem cells.The Journal of biological chemistry · 2010Article
- Sonic Hedgehog pathway activity in prostate cancer.Oncology letters · 2010Article
- Epigenetic mechanisms modulate thyroid transcription factor 1-mediated transcription of the surfactant protein B gene.The Journal of biological chemistry · 2010Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mechanisms of gene repression by transforming growth factor-beta (TGF-beta) are not well understood. TGF-beta represses transcription of pulmonary surfactant protein-B gene in lung epithelial cells. Repression is mediated by SMAD3 through interactions with NKX2.1 and FOXA1, two key transcription factors that are positive regulators of SpB transcription. In this study, we found that SMAD3 interacts through its MAD domains, MH1 and MH2 with NKX2.1 and FOXA1 proteins. The sites of interaction on NKX2.1 are located within the NH2 and COOH domains, known to be involved in transactivation function. In comparison, weaker interaction of FOXA1 winged helix, and the NH(2)-terminal domains was documented with SMAD3. Both in vitro studies and in vivo ChIP assays show that interaction of SMAD3 MH1 and MH2 domains with NKX2.1 and FOXA1 results in reduced binding of NKX2.1 and FOXA1 to their cognate DNA-binding sites, and diminished promoter occupancy within the SpB promoter. Thus, these studies reveal for the first time a mechanism of TGF-beta-induced SpB gene repression that involves interactions between specific SMAD3 domains and the corresponding functional sites on NKX2.1 and FOXA1 transcription factors.
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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.