ArticleThe Journal of biological chemistry2010
The ubiquitin ligase Nedd4-1 is required for heart development and is a suppressor of thrombospondin-1.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 72 citations in OpenAlex.
- Optimization of the recombinant overexpression and purification of human Nedd4-1 in Escherichia coli.Protein expression and purification · 2027Article
- Neural crest cell-derived DKK1 and NEDD4 modulate Wnt signalling in the second heart field to orchestrate outflow tract development.Nature communications · 2026Article
- NEDD4 promotes reactive astrogliosis by enhancing K63-linked ubiquitination and inhibiting chaperone-mediated autophagy degradation of YAP1.International journal of biological sciences · 2026Article
- Review
- Unraveling the Potential Role of NEDD4-like E3 Ligases in Cancer.International journal of molecular sciences · 2022Review
- The HECT family of E3 ubiquitin ligases and PTEN.Seminars in cancer biology · 2022Review
- Loss of NEDD4 causes complete XY gonadal sex reversal in mice.Cell death & disease · 2022Article
- The Role of HECT-Type E3 Ligase in the Development of Cardiac Disease.International journal of molecular sciences · 2021Review
- Obestatin signalling counteracts glucocorticoid-induced skeletal muscle atrophy via NEDD4/KLF15 axis.Journal of cachexia, sarcopenia and muscle · 2021Article
- Cardiac ECM: Its Epigenetic Regulation and Role in Heart Development and Repair.International journal of molecular sciences · 2020Review
- Phosphorylation Modifications Regulating Cardiac Protein Quality Control Mechanisms.Frontiers in physiology · 2020Review
- E3 Ubiquitin ligase NEDD4 family‑regulatory network in cardiovascular disease.International journal of biological sciences · 2020Review
- Regulation of the p53 Family Proteins by the Ubiquitin Proteasomal Pathway.International journal of molecular sciences · 2019Review
- Review
- Feedback regulation of RTK signaling in development.Developmental biology · 2019Review
- Monocytes and Macrophages in Heart Valves: Uninvited Guests or Critical Performers?Current opinion in biomedical engineering · 2018Article
- High-Throughput Screening of HECT E3 Ubiquitin Ligases Using UbFluor.Current protocols in chemical biology · 2017Article
- Thrombospondins: A Role in Cardiovascular Disease.International journal of molecular sciences · 2017Review
- Rare copy number variants in patients with congenital conotruncal heart defects.Birth defects research · 2017Article
- Intestinal knockout of Nedd4 enhances growth of ApcOncogene · 2016Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
Nedd4 (Nedd4-1) is a Hect domain E3 ubiquitin ligase that also contains a C2 domain and three WW domains. Despite numerous in vitro studies, its biological function in vivo is not well understood. Here we show that disruption of Nedd4-1 in mice (leaving Nedd4-2 intact) caused embryonic lethality at mid gestation, with pronounced heart defects (double-outlet right ventricle and atrioventricular cushion defects) and vasculature abnormalities. Quantitative mass spectrometry and immunoblot analyses of lysates from the wild type and knock-out mouse embryonic fibroblasts to identify Nedd4-1 in vivo targets revealed dramatically increased amounts of thrombospondin-1 (Tsp-1) in the knock-out mouse embryonic fibroblasts and embryos. Tsp-1 is an inhibitor of angiogenesis, and its elevated level was mediated primarily by enhanced transcription. Interestingly, the administration of aspirin (an inhibitor of Tsp-1) to the pregnant heterozygote mothers led to a reduction in Tsp-1 levels and a substantial rescue of the embryonic lethality. These results suggest that Nedd4-1 is a suppressor of Tsp1 and that increased levels of Tsp-1 in the Nedd4-1 knock-out mice may have contributed to the developmental defect observed in the embryos.
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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.