ArticleNucleic acids research2011
Structural basis for the cooperative DNA recognition by Smad4 MH1 dimers.
Article in Nucleic acids research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 44 citations in OpenAlex.
- Article
- Smad4 regulates TGF-β1-mediated hedgehog activation to promote epithelial-to-mesenchymal transition in pancreatic cancer cells by suppressing Gli1 activity.Computational and structural biotechnology journal · 2024Article
- Smad4 and FoxH1 potentially interact to regulate cyp19a1a promoter in the ovary of ricefield eel (Monopterus albus).Biology of sex differences · 2024Article
- Fluid shear stress-modulated chromatin accessibility reveals the mechano-dependency of endothelial SMAD1/5-mediated gene transcription.iScience · 2023Article
- Anti-Müllerian Hormone Signal Transduction involved in Müllerian Duct Regression.Frontiers in endocrinology · 2022Review
- HumanCardiogenetics · 2021Article
- Mechanism of forkhead transcription factors binding to a novel palindromic DNA site.Nucleic acids research · 2021Article
- Single cell imaging reveals cisplatin regulating interactions between transcription (co)factors and DNA.Chemical science · 2021Article
- Smad4 regulates the nuclear translocation of Nkx2-5 in cardiac differentiation.Scientific reports · 2021Article
- Consequences of Mutations and Abnormal Expression of SMAD4 in Tumors and T Cells.OncoTargets and therapy · 2021Review
- Unveiling the dimer/monomer propensities of Smad MH1-DNA complexes.Computational and structural biotechnology journal · 2021Article
- Structural basis for distinct roles of SMAD2 and SMAD3 in FOXH1 pioneer-directed TGF-β signaling.Genes & development · 2019Article
- A comparative analysis of Smad-responsive motifs identifies multiple regulatory inputs for TGF-β transcriptional activation.The Journal of biological chemistry · 2019Article
- Angiopoietin-2 Inhibition Rescues Arteriovenous Malformation in a Smad4 Hereditary Hemorrhagic Telangiectasia Mouse Model.Circulation · 2019Article
- The role of SMAD3 in the genetic predisposition to papillary thyroid carcinoma.Genetics in medicine : official journal of the American College of Medical Genetics · 2018Article
- DNA-mediated dimerization on a compact sequence signature controls enhancer engagement and regulation by FOXA1.Nucleic acids research · 2018Article
- Diversity among POU transcription factors in chromatin recognition and cell fate reprogramming.Cellular and molecular life sciences : CMLS · 2018Review
- Structural basis for genome wide recognition of 5-bp GC motifs by SMAD transcription factors.Nature communications · 2017Article
- SnoN Stabilizes the SMAD3/SMAD4 Protein Complex.Scientific reports · 2017Article
- BMP-2 induces EMT and breast cancer stemness through Rb and CD44.Cell death discovery · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Smad proteins form multimeric complexes consisting of the 'common partner' Smad4 and receptor regulated R-Smads on clustered DNA binding sites. Deciphering how pathway specific Smad complexes multimerize on DNA to regulate gene expression is critical for a better understanding of the cis-regulatory logic of TGF-β and BMP signaling. To this end, we solved the crystal structure of the dimeric Smad4 MH1 domain bound to a palindromic Smad binding element. Surprisingly, the Smad4 MH1 forms a constitutive dimer on the SBE DNA without exhibiting any direct protein-protein interactions suggesting a DNA mediated indirect readout mechanism. However, the R-Smads Smad1, Smad2 and Smad3 homodimerize with substantially decreased efficiency despite pronounced structural similarities to Smad4. Therefore, intricate variations in the DNA structure induced by different Smads and/or variant energetic profiles likely contribute to their propensity to dimerize on DNA. Indeed, competitive binding assays revealed that the Smad4/R-Smad heterodimers predominate under equilibrium conditions while R-Smad homodimers are least favored. Together, we present the structural basis for DNA recognition by Smad4 and demonstrate that Smad4 constitutively homo- and heterodimerizes on DNA in contrast to its R-Smad partner proteins by a mechanism independent of direct protein contacts.
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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.