ArticlePloS one2015
Nuclear Receptor-Like Structure and Interaction of Congenital Heart Disease-Associated Factors GATA4 and NKX2-5.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
- Combined effects of maternal periconceptional environmental exposures and infant cardiac transcription factor polymorphisms on congenital heart disease risk.Annals of medicine · 2026Article
- GATA4 Single-Amino Acid Deletion in a Male Patient With Congenital Heart Defects, Differences of Sex Development, and Diaphragmatic Hernia.Clinical genetics · 2026Article
- The Impact of Maternal Obesity and Diabetes on the Development of Congenital Heart Defects (CHDs) in Offspring: A Narrative Review.Metabolites · 2026Review
- Article
- GATA4-targeted compounds induce apoptosis and diminish viability of hepatoblastoma cells.PloS one · 2026Article
- Procollagen IIA mediates positive feedback control of the mouse cardiogenic transcriptional network.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Esketamine induces embryonic and cardiac malformation through regulating the nkx2.5 and gata4 in zebrafish.Scientific reports · 2025Article
- The molecular mechanisms of cardiac development and related diseases.Signal transduction and targeted therapy · 2024Review
- Affinity chromatography reveals direct binding of the GATA4-NKX2-5 interaction inhibitor (3i-1000) with GATA4.Scientific reports · 2024Article
- Switching of hypertrophic signalling towards enhanced cardiomyocyte identity and maturity by a GATA4-targeted compound.Stem cell research & therapy · 2024Article
- Gene editing and cardiac disease modelling for the interpretation of genetic variants of uncertain significance in congenital heart disease.Stem cell research & therapy · 2023Article
- Genetic aetiology distribution of 398 foetuses with congenital heart disease in the prenatal setting.ESC heart failure · 2023Article
- Article
- Nkx2.5: a crucial regulator of cardiac development, regeneration and diseases.Frontiers in cardiovascular medicine · 2023Review
- α1-adrenergic receptors accompanied by GATA4 expression are related to proarrhythmic conduction and automaticity in rat interatrial septum.Journal of physiology and biochemistry · 2022Article
- Overexpression of GATA binding protein 4 and myocyte enhancer factor 2C induces differentiation of mesenchymal stem cells into cardiac-like cells.World journal of stem cells · 2022Article
- Article
- GATA-targeted compounds modulate cardiac subtype cell differentiation in dual reporter stem cell line.Stem cell research & therapy · 2021Article
- Targeting GATA4 for cardiac repair.IUBMB life · 2020Review
- Synthesis, Identification, and Structure-Activity Relationship Analysis of GATA4 and NKX2-5 Protein-Protein Interaction Modulators.Journal of medicinal chemistry · 2019Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsTranscription factor GATA4 is a dosage sensitive regulator of heart development and alterations in its level or activity lead to congenital heart disease (CHD). GATA4 has also been implicated in cardiac regeneration and repair. GATA4 action involves combinatorial interaction with other cofactors such as NKX2-5, another critical cardiac regulator whose mutations also cause CHD. Despite its critical importance to the heart and its evolutionary conservation across species, the structural basis of the GATA4-NKX2-5 interaction remains incompletely understood. METHODS AND
resultsA homology model was constructed and used to identify surface amino acids important for the interaction of GATA4 and NKX2-5. These residues were subjected to site-directed mutagenesis, and the mutant proteins were characterized for their ability to bind DNA and to physically and functionally interact with NKX2-5. The studies identify 5 highly conserved amino acids in the second zinc finger (N272, R283, Q274, K299) and its C-terminal extension (R319) that are critical for physical and functional interaction with the third alpha helix of NKX2-5 homeodomain. Integration of the experimental data with computational modeling suggests that the structural arrangement of the zinc finger-homeodomain resembles the architecture of the conserved DNA binding domain of nuclear receptors.
conclusionsThe results provide novel insight into the structural basis for protein-protein interactions between two important classes of transcription factors. The model proposed will help to elucidate the molecular basis for disease causing mutations in GATA4 and NKX2-5 and may be relevant to other members of the GATA and NK classes of transcription factors.
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