ArticleMolecular and cellular biology2016
The Zinc Finger of Prolyl Hydroxylase Domain Protein 2 Is Essential for Efficient Hydroxylation of Hypoxia-Inducible Factor α.
Article in Molecular and cellular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- <p>Prolyl hydroxylase domain proteins: Localization, regulation, function and their role in erythropoiesis (Review)</p>.Molecular medicine reports · 2026Review
- A hypothesis: Potential contributions of metals to the pathogenesis of pulmonary artery hypertension.Life sciences · 2024Review
- The role of hypoxia-inducible factor 1 alpha (HIF-1α) modulation in heavy metal toxicity.Archives of toxicology · 2023Review
- Potential plasma biomarkers at low altitude for prediction of acute mountain sickness.Frontiers in immunology · 2023Article
- The ribosomal chaperone NACA recruits PHD2 to cotranslationally modify HIF-α.The EMBO journal · 2022Article
- High-Altitude Adaptation: Mechanistic Insights from Integrated Genomics and Physiology.Molecular biology and evolution · 2021Review
- Hypoxia Pathway Proteins are Master Regulators of Erythropoiesis.International journal of molecular sciences · 2020Review
- TibetanProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Update on mutations in the HIF: EPO pathway and their role in erythrocytosis.Blood reviews · 2019Review
- At the crossroads of oxygen and iron sensing: hepcidin control of HIF-2α.The Journal of clinical investigation · 2019Article
- An Erythrocytosis-Associated Mutation in the Zinc Finger of PHD2 Provides Insights into Its Binding of p23.Hypoxia (Auckland, N.Z.) · 2019Article
- Loss-of-function zinc finger mutation in theBlood · 2018Article
- Identification of Small-Molecule PHD2 Zinc Finger Inhibitors that Activate Hypoxia Inducible Factor.Chembiochem : a European journal of chemical biology · 2016Article
- Hypoxia-inducible factor 1-alpha: a dual regulator of ferroptosis in ischemic stroke and a promising therapeutic target.Frontiers in neurologyReview
- Article
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Authors and funding
5 authors at 1 institution in 1 country.
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Abstract
Prolyl hydroxylase domain protein 2 (PHD2) (also known as EGLN1) is a key oxygen sensor in mammals that posttranslationally modifies hypoxia-inducible factor α (HIF-α) and targets it for degradation. In addition to its catalytic domain, PHD2 contains an evolutionarily conserved zinc finger domain, which we have previously proposed recruits PHD2 to the HSP90 pathway to promote HIF-α hydroxylation. Here, we provide evidence that this recruitment is critical both in vitro and in vivo We show that in vitro, the zinc finger can function as an autonomous recruitment domain to facilitate interaction with HIF-α. In vivo, ablation of zinc finger function by a C36S/C42S Egln1 knock-in mutation results in upregulation of the erythropoietin gene, erythrocytosis, and augmented hypoxic ventilatory response, all hallmarks of Egln1 loss of function and HIF stabilization. Hence, the zinc finger ordinarily performs a critical positive regulatory function. Intriguingly, the function of this zinc finger is impaired in high-altitude-adapted Tibetans, suggesting that their adaptation to high altitude may, in part, be due to a loss-of-function EGLN1 allele. Thus, these findings have important implications for understanding both the molecular mechanism of the hypoxic response and human adaptation to high altitude.
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