ArticleThe Journal of biological chemistry2013
Prolyl hydroxylase domain protein 2 (PHD2) binds a Pro-Xaa-Leu-Glu motif, linking it to the heat shock protein 90 pathway.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 58 citations in OpenAlex.
- A tri-target in silico analysis of Testolift: a nutraceutical formulation targeting aromatase, myostatin, and prolyl hydroxylase-2 in testosterone regulation and muscle performance.Scientific reports · 2026Article
- Crosslinking-mediated Interactome Analysis Identified PHD2-HIF1α Interaction Hotspots and the Role of PHD2 in Regulating Protein Neddylation.bioRxiv : the preprint server for biology · 2024Article
- Hypoxia Inducible Factor pathway proteins in high-altitude mammals.Trends in biochemical sciences · 2024Review
- The role of zinc in the premature brain: functions, outcomes and future research perspectives.Frontiers in pediatrics · 2024Review
- Characterization of genetic variants in theHaematologica · 2023Article
- Genome editing and cancer therapy: handling the hypoxia-responsive pathway as a promising strategy.Cellular and molecular life sciences : CMLS · 2023Review
- High-Altitude Andean H194R HIF2A Allele Is a Hypomorphic Allele.Molecular biology and evolution · 2023Article
- The ribosomal chaperone NACA recruits PHD2 to cotranslationally modify HIF-α.The EMBO journal · 2022Article
- The multifaceted role of EGLN family prolyl hydroxylases in cancer: going beyond HIF regulation.Oncogene · 2022Review
- Targeting HIF-2α in the Tumor Microenvironment: Redefining the Role of HIF-2α for Solid Cancer Therapy.Cancers · 2022Review
- Oxygen-sensing mechanisms in development and tissue repair.Development (Cambridge, England) · 2021Review
- Hypoxia Pathway Proteins and Their Impact on the Blood Vasculature.International journal of molecular sciences · 2021Review
- Molecular Insights into the Oxygen-Sensing Pathway and Erythropoietin Expression Regulation in Erythropoiesis.International journal of molecular sciences · 2021Review
- Bidirectional Crosstalk Between Hypoxia Inducible Factors and Glucocorticoid Signalling in Health and Disease.Frontiers in immunology · 2021Review
- Cystathione β-synthase regulates HIF-1α stability through persulfidation of PHD2.Science advances · 2020Article
- TibetanProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Label-Free Interactome Analysis Revealed an Essential Role of CUL3-KEAP1 Complex in Mediating the Ubiquitination and Degradation of PHD2.Journal of proteome research · 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
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Prolyl hydroxylase domain protein 2 (PHD2, also known as Egg Laying Defective Nine homolog 1) is a key oxygen-sensing protein in metazoans. In an oxygen-dependent manner, PHD2 site-specifically prolyl hydroxylates the master transcription factor of the hypoxic response, hypoxia-inducible factor-α (HIF-α), thereby targeting HIF-α for degradation. In this report we show that the heat shock protein 90 (HSP90) co-chaperones p23 and FKBP38 interact via a conserved Pro-Xaa-Leu-Glu motif (where Xaa = any amino acid) in these proteins with the N-terminal Myeloid Nervy and DEAF-1 (MYND)-type zinc finger of PHD2. Knockdown of p23 augments hypoxia-induced HIF-1α protein levels and HIF target genes. We propose that p23 recruits PHD2 to the HSP90 machinery to facilitate HIF-1α hydroxylation. These findings identify a link between two ancient pathways, the PHD:HIF and the HSP90 pathways, and suggest that this link was established concurrent with the emergence of the PHD:HIF pathway in evolution.
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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.