ArticleThe Journal of biological chemistry2015
The E3 ubiquitin ligases, HUWE1 and NEDD4-1, are involved in the post-translational regulation of the ABCG1 and ABCG4 lipid transporters.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 51 citations in OpenAlex.
- Colchicine enhances macrophage cholesterol efflux by targeting DTL-mediated ubiquitination and degradation of ABCA1.RMD open · 2026Article
- Research Status and Latest Progress in the Regulatory Mechanisms of ABCA1.International journal of molecular sciences · 2025Review
- Multiple E3 ligases act as antiviral factors against SARS-CoV-2 via inducing the ubiquitination and degradation of ORF9b.Journal of virology · 2024Article
- The Role of Ubiquitination and the E3 Ligase Nedd4 in Regulating Corneal Epithelial Wound Healing.Investigative ophthalmology & visual science · 2024Article
- Identification and functional analysis of rare HECTD1 missense variants in human neural tube defects.Human genetics · 2024Article
- Identification and Functional Analysis of Rare HECTD1 Missense Variants in Human Neural Tube Defects.Research square · 2024Article
- HECT, UBA and WWE domain containing 1 represses cholesterol efflux during CD4Frontiers in pharmacology · 2023Article
- Transient increase in atherosclerotic plaque macrophage content followingFrontiers in cellular and infection microbiology · 2023Article
- NEDD4 attenuates phosgene-induced acute lung injury through the inhibition of Notch1 activation.Journal of cellular and molecular medicine · 2022Article
- The Ubiquitin E3 Ligase Nedd4 Regulates the Expression and Amyloid-β Peptide Export Activity of P-Glycoprotein.International journal of molecular sciences · 2022Article
- Ubiquitinated ligation protein NEDD4L participates in MiR-30a-5p attenuated atherosclerosis by regulating macrophage polarization and lipid metabolism.Molecular therapy. Nucleic acids · 2021Article
- SFPQ rescues F508del-CFTR expression and function in cystic fibrosis bronchial epithelial cells.Scientific reports · 2021Article
- E3 Ubiquitin Ligases as Immunotherapeutic Target in Atherosclerotic Cardiovascular Disease.Frontiers in cardiovascular medicine · 2020Review
- miR‑146a‑5p suppresses ATP‑binding cassette subfamily G member 1 dysregulation in patients with refractory Mycoplasma pneumoniae via interleukin 1 receptor‑associated kinase 1 downregulation.International journal of molecular medicine · 2019Article
- Potential molecular mechanism of ACE gene at different time points in STEMI patients based on genome-wide microarray dataset.Lipids in health and disease · 2019Article
- Meta-analysis of gene expression alterations and clinical significance of the HECT domain-containing ubiquitin ligase HUWE1 in cancer.Oncology letters · 2019Article
- The Adaptor Protein Alix is Involved in the Interaction Between the Ubiquitin Ligase NEDD4-1 and its Targets, ABCG1 and ABCG4.International journal of molecular sciences · 2019Article
- The SCFFBXO3 ubiquitin E3 ligase regulates inflammation in atherosclerosis.Journal of molecular and cellular cardiology · 2019Article
- Protease-activated receptor 1 inhibits cholesterol efflux and promotes atherogenesis via cullin 3-mediated degradation of the ABCA1 transporter.The Journal of biological chemistry · 2018Article
- 6-Dihydroparadol, a Ginger Constituent, Enhances Cholesterol Efflux from THP-1-Derived Macrophages.Molecular nutrition & food research · 2018Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ATP-binding cassette transporter ABCG1 has an essential role in cellular cholesterol homeostasis, and dysregulation has been associated with a number of high burden diseases. Previous studies reported that ABCG1 is ubiquitinated and degraded via the ubiquitin proteasome system. However, so far the molecular mechanism, including the identity of any of the rate-limiting ubiquitination enzymes, or E3 ligases, is unknown. Using liquid chromatography mass spectrometry, we identified two HECT domain E3 ligases associated with ABCG1, named HUWE1 (HECT, UBA, and WWE domain containing 1, E3 ubiquitin protein ligase) and NEDD4-1 (Neural precursor cell-expressed developmentally down regulated gene 4), of which the latter is the founding member of the NEDD4 family of ubiquitin ligases. Silencing both HUWE1 and NEDD4-1 in cells overexpressing human ABCG1 significantly increased levels of the ABCG1 monomeric and dimeric protein forms, however ABCA1 protein expression was unaffected. In addition, ligase silencing increased ABCG1-mediated cholesterol export to HDL in cells overexpressing the transporter as well as in THP-1 macrophages. Reciprocally, overexpression of both ligases resulted in a significant reduction in protein levels of both the ABCG1 monomeric and dimeric forms. Like ABCG1, ABCG4 protein levels and cholesterol export activity were significantly increased after silencing both HUWE1 and NEDD4-1 in cells overexpressing this closely related ABC half-transporter. In summary, we have identified for the first time two E3 ligases that are fundamental enzymes in the post-translational regulation of ABCG1 and ABCG4 protein levels and cellular cholesterol export activity.
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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.