ArticleBiochimica et biophysica acta2011
NOTCH1 missense alleles associated with left ventricular outflow tract defects exhibit impaired receptor processing and defective EMT.
Article in Biochimica et biophysica acta, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- ALPK3 regulates cardiomyocyte apoptosis through the Notch1 signaling pathway.Molecular genetics and genomics : MGG · 2026Article
- Common Coronary Artery Disease Risk Variants in Endothelial Regulatory Elements Modulate Tetraspanin 14 Expression and Notch Signaling.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Cardiac EndMT and EpiMT as a developmental continuum: integration of mechanical, metabolic, and epigenetic regulation.Frontiers in cell and developmental biology · 2026Review
- Bicuspid Aortic Valve: Old and Novel Gene Contribution to Disease Onset and Complications.Diagnostics (Basel, Switzerland) · 2025Article
- Impaired Human Cardiac Cell Development due to NOTCH1 Deficiency.Circulation research · 2023Article
- Probing single ventricle heart defects with patient-derived induced pluripotent stem cells and emerging technologies.Birth defects research · 2022Review
- Exome sequencing in multiplex families with left-sided cardiac defects has high yield for disease gene discovery.PLoS genetics · 2022Article
- SNP and DNA methylation analyses of a monozygotic twins discordant for complete endocardial cushion defect: a case report.American journal of translational research · 2022Article
- Aortic root aortopathy in bicuspid aortic valve associated with high genetic risk.BMC cardiovascular disorders · 2021Article
- Decoding Genetics of Congenital Heart Disease Using Patient-Derived Induced Pluripotent Stem Cells (iPSCs).Frontiers in cell and developmental biology · 2021Review
- Loss of function, missense, and intronic variants in NOTCH1 confer different risks for left ventricular outflow tract obstructive heart defects in two European cohorts.Genetic epidemiology · 2019Article
- A novel Notch1 missense mutation (C1133Y) in the Abruptex domain exhibits enhanced proliferation and invasion in oral squamous cell carcinoma.Cancer cell international · 2018Article
- A genome-wide association study of congenital cardiovascular left-sided lesions shows association with a locus on chromosome 20.Human molecular genetics · 2016Article
- Compound heterozygous NOTCH1 mutations underlie impaired cardiogenesis in a patient with hypoplastic left heart syndrome.Human genetics · 2015Article
- MATR3 disruption in human and mouse associated with bicuspid aortic valve, aortic coarctation and patent ductus arteriosus.Human molecular genetics · 2015Article
- Role of Notch signaling in the mammalian heart.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2014Review
- Notch signaling in human development and disease.Seminars in cell & developmental biology · 2012Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Notch signaling is essential for proper cardiac development. We recently identified missense variants in the NOTCH1 receptor in patients with diverse left ventricular outflow tract (LVOT) malformations (NOTCH1(G661S) and NOTCH1(A683T)) that reduce ligand-induced Notch signaling. Here, we examine the molecular mechanisms that contribute to reduced signaling and perturbed development. We find that NOTCH1(A683T) exhibits reduced S1 cleavage due to impaired trafficking through the endoplasmic reticulum (ER). This observation is consistent with improper localization of the variant receptor to the ER and decreased presentation at the cell surface. In contrast, the nearby mutation NOTCH1(G661S) exhibits reduced cell-surface presentation in the absence of overt folding or trafficking defects. To examine the implications of these variants in disease pathogenesis, we investigated their effect on epithelial-to-mesenchymal transition (EMT), a critical process for development of the outflow tract. We find that these LVOT-associated NOTCH1 alleles can contribute to defective EMT in endothelial cell lines through impaired induction of Snail and Hes family members. These data represent the first description of a molecular mechanism underlying NOTCH1 mutations in individuals with LVOT malformations, and have important implications regarding the functional contribution of these alleles to a complex set of developmental defects.
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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.