ArticleThe Biochemical journal2007
Hypoxia-induced assembly of prolyl hydroxylase PHD3 into complexes: implications for its activity and susceptibility for degradation by the E3 ligase Siah2.
Article in The Biochemical journal, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 56 citations in OpenAlex.
- EGLN1 prolyl hydroxylation of hypoxia-induced transcription factor HIF1α is repressed by SET7-catalyzed lysine methylation.The Journal of biological chemistry · 2022Article
- Discovery, characterization and potential roles of a novel NF-YAx splice variant in human neuroblastoma.Journal of experimental & clinical cancer research : CR · 2019Article
- Prolyl 4-Hydroxylase Domain Protein 3-Inhibited Smooth-Muscle-Cell Dedifferentiation Improves Cardiac Perivascular Fibrosis Induced by Obstructive Sleep Apnea.BioMed research international · 2019Article
- The role of E3 ubiquitin ligase seven in absentia homolog in the innate immune system: An overview.Veterinary world · 2018Review
- Infarct size-limiting effect of epoxyeicosatrienoic acid analog EET-B is mediated by hypoxia-inducible factor-1α via downregulation of prolyl hydroxylase 3.American journal of physiology. Heart and circulatory physiology · 2018Article
- Enhanced angiogenesis, hypoxia and neutrophil recruitment during Myc-induced liver tumorigenesis in zebrafish.Scientific reports · 2016Article
- Molecular mechanisms of action and therapeutic uses of pharmacological inhibitors of HIF-prolyl 4-hydroxylases for treatment of ischemic diseases.Antioxidants & redox signaling · 2014Review
- Fine tuning of the UPR by the ubiquitin ligases Siah1/2.PLoS genetics · 2014Article
- Prolyl hydroxylase domain enzymes: important regulators of cancer metabolism.Hypoxia (Auckland, N.Z.) · 2014Review
- Investigating the molecular basis of Siah1 and Siah2 E3 ubiquitin ligase substrate specificity.PloS one · 2014Article
- Prolyl-hydroxylase 3: Evolving Roles for an Ancient Signaling Protein.Hypoxia (Auckland, N.Z.) · 2013Article
- EGLN3 inhibition of NF-κB is mediated by prolyl hydroxylase-independent inhibition of IκB kinase γ ubiquitination.Molecular and cellular biology · 2013Article
- Seven in absentia homolog 2 (Siah2) protein is a regulator of NF-E2-related factor 2 (Nrf2).The Journal of biological chemistry · 2013Article
- The ubiquitin ligase Siah2 regulates PPARγ activity in adipocytes.Endocrinology · 2012Article
- von Hippel-Lindau-dependent patterns of RNA polymerase II hydroxylation in human renal clear cell carcinomas.Clinical cancer research : an official journal of the American Association for Cancer Research · 2010Article
- Abnormalities in oxygen sensing define early and late onset preeclampsia as distinct pathologies.PloS one · 2010Article
- BRCA1 tumours correlate with a HIF-1alpha phenotype and have a poor prognosis through modulation of hydroxylase enzyme profile expression.British journal of cancer · 2009Article
- Hypoxia-inducible factor prolyl-4-hydroxylase PHD2 protein abundance depends on integral membrane anchoring of FKBP38.The Journal of biological chemistry · 2009Article
- The ubiquitin ligase Siah2 and the hypoxia response.Molecular cancer research : MCR · 2009Review
- Inhibition of Siah ubiquitin ligase function.Oncogene · 2009Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
PHD1-3 (prolyl hydroxylases 1-3) catalyse the hydroxylation of HIF (hypoxia-inducible factor)-alpha subunit that triggers the substrate ubiquitination and subsequent degradation. The RING (really interesting new gene) finger E3 ligase Siah2 preferentially targets PHD3 for degradation. Here, we identify the requirements for such selective targeting. Firstly, PHD3 lacks an N-terminal extension found in PHD1 and PHD2; deletion of this domain from PHD1 and PHD2 renders them susceptible to degradation by Siah2. Secondly, PHD3 can homo- and hetero-multimerize with other PHDs. Consequently, PHD3 is found in high-molecular-mass fractions that were enriched in hypoxia. Interestingly, within the lower-molecular-mass complex, PHD3 exhibits higher specific activity towards hydroxylation of HIF-1alpha and co-localizes with Siah2, suggesting that Siah2 limits the availability of the more active form of PHD3. These findings provide new insight into the mechanism underlying the regulation of PHD3 availability and activity in hypoxia by the E3 ligase Siah2.
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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.