ArticleScientific reports2017
A HAND to TBX5 Explains the Link Between Thalidomide and Cardiac Diseases.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- Safety considerations for cereblon-recruiting targeted protein degraders.Nature reviews. Drug discovery · 2026Review
- Possible New Candidates Involved to Thalidomide-Related Limbs and Cardiac Defects: A Systems Biology Approach.Biochemical genetics · 2025Article
- Transformative Potential of Induced Pluripotent Stem Cells in Congenital Heart Disease Research and Treatment.Children (Basel, Switzerland) · 2025Review
- Thalidomide-induced limb malformations: an update and reevaluation.Archives of toxicology · 2025Review
- In Vitro Models of Cardiovascular Disease: Embryoid Bodies, Organoids and Everything in Between.Biomedicines · 2024Review
- HAND factors regulate cardiac lineage commitment and differentiation from human pluripotent stem cells.Stem cell research & therapy · 2024Article
- A New Strategy for the Old Challenge of Thalidomide: Systems Biology Prioritization of Potential Immunomodulatory Drug (IMiD)-Targeted Transcription Factors.International journal of molecular sciences · 2023Article
- Cohesin: an emerging master regulator at the heart of cardiac development.Molecular biology of the cell · 2023Article
- Socioeconomic, Ethnocultural, Substance- and Cannabinoid-Related Epidemiology of Down Syndrome USA 1986-2016: Combined Geotemporospatial and Causal Inference Investigation.International journal of environmental research and public health · 2022Observational
- Epigenetics and Congenital Heart Diseases.Journal of cardiovascular development and disease · 2022Review
- The TH1 cell lineage-determining transcription factor T-bet suppresses TH2 gene expression by redistributing GATA3 away from TH2 genes.Nucleic acids research · 2022Article
- Cancer Chemotherapy-Induced Sinus Bradycardia: A Narrative Review of a Forgotten Adverse Effect of Cardiotoxicity.Drug safety · 2022Review
- Post-marketing safety of immunomodulatory drugs in multiple myeloma: A pharmacovigilance investigation based on the FDA adverse event reporting system.Frontiers in pharmacology · 2022Article
- A genome-wide association analysis for body weight at 35 days measured on 137,343 broiler chickens.Genetics, selection, evolution : GSE · 2021Article
- Article
- The role of ESCO2, SALL4 and TBX5 genes in the susceptibility to thalidomide teratogenesis.Scientific reports · 2019Article
- Portrait of Tissue-Specific Coexpression Networks of Noncoding RNAs (miRNA and lncRNA) and mRNAs in Normal Tissues.Computational and mathematical methods in medicine · 2019Article
- Thalidomide remodels developing heart in chick embryo: discovery of a thalidomide mediated hematoma in heart muscle.Naunyn-Schmiedeberg's archives of pharmacology · 2018Article
- Transcriptomic Alterations in Lung Adenocarcinoma Unveil New Mechanisms Targeted by theFrontiers in oncology · 2018Article
- Single-Construct Polycistronic Doxycycline-Inducible Vectors Improve Direct Cardiac Reprogramming and Can Be Used to Identify the Critical Timing of Transgene Expression.International journal of molecular sciences · 2017Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Congenital heart disease is the leading cause of death in the first year of life. Mutations only in few genes have been linked to some cases of CHD. Thalidomide was used by pregnant women for morning sickness but was removed from the market because it caused severe malformations including CHDs. We used both in silico docking software, and in vitro molecular and biochemical methods to document a novel interaction involving Thalidomide, TBX5, and HAND2. Thalidomide binds readily to TBX5 through amino acids R81, R82, and K226 all implicated in DNA binding. It reduces TBX5 binding to DNA by 40%, and suppresses TBX5 mediated activation of the NPPA and VEGF promoters by 70%. We documented a novel interaction between TBX5 and HAND2, and showed that a p.G202V HAND2 variant associated with CHD and coronary artery diseases found in a large Lebanese family with high consanguinity, drastically inhibited this interaction by 90%. Similarly, thalidomide inhibited the TBX5/HAND2 physical interaction, and the in silico docking revealed that the same amino acids involved in the interaction of TBX5 with DNA are also involved in its binding to HAND2. Our results establish a HAND2/TBX5 pathway implicated in heart development and diseases.
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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.