ArticleCell discovery2016
Hypertension-associated C825T polymorphism impairs the function of Gβ3 to target GRK2 ubiquitination.
Article in Cell discovery, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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Who cites it
12 citing papers in PubMed, 14 citations in OpenAlex.
- G protein-coupled receptor kinases in hypertension: physiology, pathogenesis, and therapeutic targets.Hypertension research : official journal of the Japanese Society of Hypertension · 2024Review
- Review
- Identification of hypertrophy-modulating Cullin-RING ubiquitin ligases in primary cardiomyocytes.Frontiers in physiology · 2023Article
- Summary of Known Genetic and Epigenetic Modification Contributed to Hypertension.International journal of hypertension · 2023Review
- Targeting G protein-coupled receptor kinases (GRKs) to G protein-coupled receptors.Current opinion in endocrine and metabolic research · 2021Article
- The Role of Cullin-RING Ligases in Striated Muscle Development, Function, and Disease.International journal of molecular sciences · 2020Review
- Analysis of HCRTR2, GNB3, and ADH4 Gene Polymorphisms in a Southeastern European Caucasian Cluster Headache Population.Journal of molecular neuroscience : MN · 2020Article
- G protein-coupled receptor kinase 2 (GRK2) as a multifunctional signaling hub.Cellular and molecular life sciences : CMLS · 2019Review
- Single Nucleotide Polymorphisms in Chemosensory Pathway Genes GNB3, TAS2R19, and TAS2R38 Are Associated with Chronic Rhinosinusitis.International archives of allergy and immunology · 2019Article
- The emerging role for Cullin 4 family of E3 ligases in tumorigenesis.Biochimica et biophysica acta. Reviews on cancer · 2019Review
- Is GRK2 a new target for cardiovascular disease?Hypertension research : official journal of the Japanese Society of Hypertension · 2018Article
- Functional analysis of Cullin 3 E3 ligases in tumorigenesis.Biochimica et biophysica acta. Reviews on cancer · 2018Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Population-based and case-control studies in different ethnicities have linked a polymorphism, C825T, in exon 10 of GNB3 gene to hypertension and several additional diseases. The 825T allele is associated with alternative splicing and results in a shortened Gβ3 protein, referred to as Gβ3s, which loses 41 amino acids encompassing one WD40 repeat domain. The mechanism of how Gβ3 C825T polymorphism is associated with hypertension has remained unclear, but an impairment of its canonical function in G-protein-coupled receptor signaling has been ruled out. Here, we report that Gβ3, like other Gβ proteins, binds to DDB1 and assembles a DDB1-CUL4A-ROC1 E3 ubiquitin ligase (CRL4A(Gβ3)) to target GRK2 ubiquitination. The loss of the 41 amino-acid residues disrupts the Gβ3-DDB1 binding and impairs the function of Gβ3s to ubiquitinate GRK2. GRK2 ubiquitination levels were decreased and protein levels were accumulated in the blood samples of Gβ3 825T allele carriers. Deletion of Cul4a in mice resulted in systolic pressure increased and weakened heart function in male mice that can be partially rescued by the deletion of one Grk2 allele. These results reveal a mechanism explaining the link between Gβ3 C825T polymorphism and hypertension.
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Registered trials
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