ArticleScience signaling2009
Oxygen-regulated beta(2)-adrenergic receptor hydroxylation by EGLN3 and ubiquitylation by pVHL.
Article in Science signaling, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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Who cites it
94 citing papers in PubMed, 151 citations in OpenAlex.
- Stress‑induced catecholamines attenuate sorafenib efficacy by inhibiting ferroptosis in β2‑adrenergic receptor positive renal cell carcinoma.International journal of oncology · 2026Article
- S-nitrosylation of pVHL regulates βProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Loss of VHL-mediated pRb regulation promotes clear cell renal cell carcinoma.Cell death & disease · 2025Article
- SOCS domain targets ECM assembly in lung fibroblasts and experimental lung fibrosis.Scientific reports · 2024Article
- Multiple-Wave Admixture and Adaptive Evolution of the Pamirian Wakhi People.Molecular biology and evolution · 2024Article
- Surgical Management and Long-Term Evaluation of Pancreatic Neuroendocrine Tumors.The Surgical clinics of North America · 2024Review
- Recent Advances and Therapeutic Implications of 2-Oxoglutarate-Dependent Dioxygenases in Ischemic Stroke.Molecular neurobiology · 2024Review
- SOCS domain targets ECM assembly in lung fibroblasts and experimental lung fibrosis.bioRxiv : the preprint server for biology · 2024Article
- In vivo protein turnover rates in varying oxygen tensions nominate MYBBP1A as a mediator of the hyperoxia response.Science advances · 2023Article
- PHD3 inhibits colon cancer cell metastasis through the occludin-p38 pathway.Acta biochimica et biophysica Sinica · 2023Article
- Function, mechanism and drug discovery of ubiquitin and ubiquitin-like modification with multiomics profiling for cancer therapy.Acta pharmaceutica Sinica. B · 2023Review
- Hypoxia and HIF-1α Regulate the Activity and Expression of Na,K-ATPase Subunits in H9c2 Cardiomyoblasts.Current issues in molecular biology · 2023Article
- Review
- Hypoxic Stress-Dependent Regulation of Na,K-ATPase in Ischemic Heart Disease.International journal of molecular sciences · 2023Review
- Potential Treatment Strategies for Hepatocellular Carcinoma Cell Sensitization to Sorafenib.Journal of hepatocellular carcinoma · 2023Review
- Impaired oxygen-sensitive regulation of mitochondrial biogenesis within the von Hippel-Lindau syndrome.Nature metabolism · 2022Article
- PHD3 inhibits cell proliferation through hydroxylation of PAX2 at proline 9.Acta biochimica et biophysica Sinica · 2022Article
- Clinical Potential of Hypoxia Inducible Factors Prolyl Hydroxylase Inhibitors in Treating Nonanemic Diseases.Frontiers in pharmacology · 2022Review
- Article
- Tumor-associated antigen Prame targets tumor suppressor p14/ARF for degradation as the receptor protein of CRL2Cell death and differentiation · 2021Article
34 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Agonist-induced ubiquitylation and degradation of heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) play an essential role in surface receptor homeostasis, thereby tuning many physiological processes. Although beta-arrestin and affiliated E3 ligases mediate agonist-stimulated lysosomal degradation of the beta(2)-adrenergic receptor (beta(2)AR), a prototypic GPCR, the molecular cues that mark receptors for ubiquitylation and the regulation of receptor degradation by the proteasome remain poorly understood. We show that the von Hippel-Lindau tumor suppressor protein (pVHL)-E3 ligase complex, known for its regulation of hypoxia-inducible factor (HIF) proteins, interacts with and ubiquitylates the beta(2)AR, thereby decreasing receptor abundance. We further show that the interaction of pVHL with beta(2)AR is dependent on proline hydroxylation (proline-382 and -395) and that the dioxygenase EGLN3 interacts directly with the beta(2)AR to serve as an endogenous beta(2)AR prolyl hydroxylase. Under hypoxic conditions, receptor hydroxylation and subsequent ubiquitylation decrease dramatically, thus attenuating receptor degradation and down-regulation. Notably, in both cells and tissue, the abundance of endogenous beta(2)AR is shown to reflect constitutive turnover by EGLN3 and pVHL. Our findings provide insight into GPCR regulation, broaden the functional scope of prolyl hydroxylation, and expand our understanding of the cellular response to hypoxia.
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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.