EGLN1

Summary

Gene Symbol: EGLN1
Description: egl nine homolog 1 (C. elegans)
Alias: C1orf12, ECYT3, HIF-PH2, HIFPH2, HPH-2, HPH2, PHD2, SM20, ZMYND6, HIF prolyl hydroxylase 2, HIF-prolyl hydroxylase 2, egl nine homolog 1, egl nine-like protein 1, hypoxia-inducible factor prolyl hydroxylase 2, prolyl hydroxylase domain-containing protein 2, zinc finger MYND domain-containing protein 6
Species: human

Top Publications

  1. ncbi Tumor vasculature is regulated by PHD2-mediated angiogenesis and bone marrow-derived cell recruitment
    Denise A Chan
    Center for Clinical Sciences Research, Department of Radiation Oncology, Stanford University, Stanford, CA 94305, USA
    Cancer Cell 15:527-38. 2009
  2. ncbi PHDs overactivation during chronic hypoxia "desensitizes" HIFalpha and protects cells from necrosis
    Amandine Ginouves
    Institute of Signaling, Developmental Biology, and Cancer Research, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6543, University of Nice, Centre Antoine Lacassagne, 06189 Nice, France
    Proc Natl Acad Sci U S A 105:4745-50. 2008
  3. ncbi A conserved family of prolyl-4-hydroxylases that modify HIF
    R K Bruick
    Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard L3 124, Dallas, TX 75390 9152, USA
    Science 294:1337-40. 2001
  4. ncbi Regulation of HIF prolyl hydroxylases by hypoxia-inducible factors
    Olga Aprelikova
    Laboratory of Biosystems and Cancer, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA
    J Cell Biochem 92:491-501. 2004
  5. ncbi Cellular oxygen sensing: Crystal structure of hypoxia-inducible factor prolyl hydroxylase (PHD2)
    Michael A McDonough
    Oxford Centre for Molecular Sciences and Department of Chemistry, University of Oxford, Mansfield Road, Oxford OX1 3TA, United Kingdom
    Proc Natl Acad Sci U S A 103:9814-9. 2006
  6. ncbi Differential function of the prolyl hydroxylases PHD1, PHD2, and PHD3 in the regulation of hypoxia-inducible factor
    Rebecca J Appelhoff
    Henry Wellcome Bldg of Genomic Medicine, Roosevelt Drive, Headington, Oxford, UK
    J Biol Chem 279:38458-65. 2004
  7. ncbi Regulation of the prolyl hydroxylase domain protein 2 (phd2/egln-1) gene: identification of a functional hypoxia-responsive element
    Eric Metzen
    Institute of Physiology, University of Luebeck, Ratzeburger Allee 160, D23538 Luebeck, Germany
    Biochem J 387:711-7. 2005
  8. ncbi Differential regulation of HIF-1 alpha prolyl-4-hydroxylase genes by hypoxia in human cardiovascular cells
    Catherine L Cioffi
    Department of Metabolic and Cardiovascular Diseases, Novartis Institute for Biomedical Research, 556 Morris Avenue, Summit, NJ 07901, USA
    Biochem Biophys Res Commun 303:947-53. 2003
  9. ncbi A novel erythrocytosis-associated PHD2 mutation suggests the location of a HIF binding groove
    Melanie J Percy
    Department of Haematology, Belfast City Hospital, Belfast, United Kingdom
    Blood 110:2193-6. 2007
  10. ncbi Endothelin-1 inhibits prolyl hydroxylase domain 2 to activate hypoxia-inducible factor-1alpha in melanoma cells
    Francesca Spinella
    Laboratory of Molecular Pathology, Regina Elena National Cancer Institute, Rome, Italy
    PLoS ONE 5:e11241. 2010

Research Grants

  1. Mechanisms of Hyperbaric Oxygen Induced Brain Protection
    John H Zhang; Fiscal Year: 2010
  2. Molecular Imaging of Targeted Cardiac Gene Therapy
    Joseph C Wu; Fiscal Year: 2010
  3. Regulation of the cullin family E3 ubiquitin ligases
    Zhen Qiang Pan; Fiscal Year: 2007
  4. Regulation of the cullin family E3 ubiquitin ligases
    Zhen Qiang Pan; Fiscal Year: 2006
  5. Regulation of vascular maturation/regression in diabetes
    Jian xiong Chen; Fiscal Year: 2010
  6. Functional Analysis of the Von Hippel-Lindau Protein
    William G Kaelin; Fiscal Year: 2010
  7. Functional Analysis of the Von Hippel-Lindau Protein
    William Kaelin; Fiscal Year: 2009
  8. Functional Analysis of the Von Hippel-Lindau Protein
    William Kaelin; Fiscal Year: 2009
  9. Functional Analysis of the Von Hippel-Lindau Protein
    William Kaelin; Fiscal Year: 2007
  10. Molecular Mechanisms of the Hypoxic Response
    Frank S Lee; Fiscal Year: 2010

Scientific Experts

Detail Information

Publications136 found, 100 shown here

  1. ncbi Tumor vasculature is regulated by PHD2-mediated angiogenesis and bone marrow-derived cell recruitment
    Denise A Chan
    Center for Clinical Sciences Research, Department of Radiation Oncology, Stanford University, Stanford, CA 94305, USA
    Cancer Cell 15:527-38. 2009
    ..These two factors are regulated by PHD2 in a HIF-independent but NF-kappaB-dependent manner...
  2. ncbi PHDs overactivation during chronic hypoxia "desensitizes" HIFalpha and protects cells from necrosis
    Amandine Ginouves
    Institute of Signaling, Developmental Biology, and Cancer Research, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6543, University of Nice, Centre Antoine Lacassagne, 06189 Nice, France
    Proc Natl Acad Sci U S A 105:4745-50. 2008
    ..Hence, PHDs serve as dual enzymes, for which inactivation and later overactivation is necessary for cell survival in acute or chronic hypoxia, respectively...
  3. ncbi A conserved family of prolyl-4-hydroxylases that modify HIF
    R K Bruick
    Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard L3 124, Dallas, TX 75390 9152, USA
    Science 294:1337-40. 2001
    ..These findings indicate that HPH is an essential component of the pathway through which cells sense oxygen...
  4. ncbi Regulation of HIF prolyl hydroxylases by hypoxia-inducible factors
    Olga Aprelikova
    Laboratory of Biosystems and Cancer, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA
    J Cell Biochem 92:491-501. 2004
    ..In contrast, we demonstrate that PHD2 is not affected by overexpression or downregulation of HIF-2alpha...
  5. ncbi Cellular oxygen sensing: Crystal structure of hypoxia-inducible factor prolyl hydroxylase (PHD2)
    Michael A McDonough
    Oxford Centre for Molecular Sciences and Department of Chemistry, University of Oxford, Mansfield Road, Oxford OX1 3TA, United Kingdom
    Proc Natl Acad Sci U S A 103:9814-9. 2006
    ..We describe crystal structures of the catalytic domain of human PHD2, an important prolyl-4-hydroxylase in the human hypoxic response in normal cells, in complex with Fe(II) and an ..
  6. ncbi Differential function of the prolyl hydroxylases PHD1, PHD2, and PHD3 in the regulation of hypoxia-inducible factor
    Rebecca J Appelhoff
    Henry Wellcome Bldg of Genomic Medicine, Roosevelt Drive, Headington, Oxford, UK
    J Biol Chem 279:38458-65. 2004
    ..Although three HIF prolyl hydroxylases, PHD1, PHD2, and PHD3, have been identified that have the potential to catalyze this reaction, the contribution of each isoform ..
  7. ncbi Regulation of the prolyl hydroxylase domain protein 2 (phd2/egln-1) gene: identification of a functional hypoxia-responsive element
    Eric Metzen
    Institute of Physiology, University of Luebeck, Ratzeburger Allee 160, D23538 Luebeck, Germany
    Biochem J 387:711-7. 2005
    ..RNA interference directed against PHD2, but not PHD1 or PHD3, is sufficient to stabilize HIF-1alpha in normoxia...
  8. ncbi Differential regulation of HIF-1 alpha prolyl-4-hydroxylase genes by hypoxia in human cardiovascular cells
    Catherine L Cioffi
    Department of Metabolic and Cardiovascular Diseases, Novartis Institute for Biomedical Research, 556 Morris Avenue, Summit, NJ 07901, USA
    Biochem Biophys Res Commun 303:947-53. 2003
    Three HIF-alpha prolyl-4-hydroxylases (PHDs) (named PHD1, PHD2, and PHD3) effect the proteasome-mediated degradation of HIF by catalyzing the hydroxylation of key proline residues in the HIF-1 alpha subunit under normoxic conditions...
  9. ncbi A novel erythrocytosis-associated PHD2 mutation suggests the location of a HIF binding groove
    Melanie J Percy
    Department of Haematology, Belfast City Hospital, Belfast, United Kingdom
    Blood 110:2193-6. 2007
    ..Several mutations in VHL have been reported in erythrocytosis, but only 1 mutation in the HIF prolyl hydroxylase PHD2 (prolyl hydroxylase domain protein 2) has been described...
  10. ncbi Endothelin-1 inhibits prolyl hydroxylase domain 2 to activate hypoxia-inducible factor-1alpha in melanoma cells
    Francesca Spinella
    Laboratory of Molecular Pathology, Regina Elena National Cancer Institute, Rome, Italy
    PLoS ONE 5:e11241. 2010
    ....
  11. ncbi Transforming growth factor beta1 induces hypoxia-inducible factor-1 stabilization through selective inhibition of PHD2 expression
    Stephanie McMahon
    Immunology Division, Faculty of Medicine, Universite de Sherbrooke, Sherbrooke, Quebec, Canada
    J Biol Chem 281:24171-81. 2006
    ..and specifically decreases both mRNA and protein levels of a HIF-1alpha-associated prolyl hydroxylase (PHD), PHD2, through the Smad signaling pathway...
  12. ncbi Nitric oxide modulates oxygen sensing by hypoxia-inducible factor 1-dependent induction of prolyl hydroxylase 2
    Utta Berchner-Pfannschmidt
    Institut fur Physiologie, Universitat Duisburg Essen, Hufelandstrasse 55, D 45122 Essen, Germany
    J Biol Chem 282:1788-96. 2007
    ..NO induces expression of PHD2 and -3 mRNA and protein under normoxia and hypoxia in a strictly HIF-1-dependent manner...
  13. ncbi Intracellular localisation of human HIF-1 alpha hydroxylases: implications for oxygen sensing
    Eric Metzen
    Institute of Physiology, University of Lubeck, Ratzeburger Allee 160, D 23538 Lubeck, Germany
    J Cell Sci 116:1319-26. 2003
    ..Three human oxygen-dependent HIF-1 alpha prolyl hydroxylases (PHD1, PHD2, and PHD3) function as oxygen sensors in vivo...
  14. ncbi A family with erythrocytosis establishes a role for prolyl hydroxylase domain protein 2 in oxygen homeostasis
    Melanie J Percy
    Department of Haematology, Belfast City Hospital, Belfast BT9 7AB, Northern Ireland, United Kingdom
    Proc Natl Acad Sci U S A 103:654-9. 2006
    ..Here we describe an inherited mutation in a mammalian PHD enzyme. We show that this mutation in PHD2 results in a marked decrease in enzyme activity and is associated with familial erythrocytosis, identifying a ..
  15. ncbi Prolyl hydroxylase 2 deficiency limits proliferation of vascular smooth muscle cells by hypoxia-inducible factor-1{alpha}-dependent mechanisms
    Kelly Schultz
    Molecular Cardiology Research Institute, Department of Medicine, Tufts Medical Center, Boston, Massachusetts, USA
    Am J Physiol Lung Cell Mol Physiol 296:L921-7. 2009
    ..Here, we tested the hypothesis that PHD2, a prolyl hydroxylase domain (PHD)-containing O(2) sensor, modulates growth factor-induced proliferative responses ..
  16. ncbi HIF-1, O(2), and the 3 PHDs: how animal cells signal hypoxia to the nucleus
    G L Semenza
    McKusick Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Cell 107:1-3. 2001
    ..A molecular basis for O(2)-regulated expression of the HIF-1 alpha subunit has now been determined, providing a mechanism for changes in gene expression in response to changes in cellular oxygenation...
  17. ncbi HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1alpha in normoxia
    Edurne Berra
    Institute of Signaling, Developmental Biology and Cancer Research, CNRS UMR 6543, Centre Antoine Lacassagne, 33 Avenue Valombrose, 06189 Nice, France
    EMBO J 22:4082-90. 2003
    ..Here we show that specific 'silencing' of PHD2 with short interfering RNAs is sufficient to stabilize and activate HIF-1alpha in normoxia in all the human cells ..
  18. ncbi Metastasis-associated protein 1 enhances stability of hypoxia-inducible factor-1alpha protein by recruiting histone deacetylase 1
    Young Gun Yoo
    College of Pharmacy and Bio MAX Institute, Seoul National University, Seoul, Korea
    EMBO J 25:1231-41. 2006
    ....
  19. ncbi The new tumor-suppressor gene inhibitor of growth family member 4 (ING4) regulates the production of proangiogenic molecules by myeloma cells and suppresses hypoxia-inducible factor-1 alpha (HIF-1alpha) activity: involvement in myeloma-induced angiogenesi
    Simona Colla
    Hematology and Bone Marrow Transplantation Center, University of Parma, Parma, Italy
    Blood 110:4464-75. 2007
    ..A direct interaction between ING4 and the HIF prolyl hydroxylase 2 (HPH-2) was also demonstrated...
  20. ncbi Investigating the dependence of the hypoxia-inducible factor hydroxylases (factor inhibiting HIF and prolyl hydroxylase domain 2) on ascorbate and other reducing agents
    Emily Flashman
    Chemistry Research Laboratory and the Oxford Centre for Integrative Systems Biology, University of Oxford, Mansfield Road, Oxford OX13TA, U K
    Biochem J 427:135-42. 2010
    ..We have investigated the ascorbate dependence of PHD2-catalysed hydroxylation of two prolyl hydroxylation sites in human HIF-1alpha, and of FIH-catalysed hydroxylation ..
  21. ncbi Ang-1 gene therapy inhibits hypoxia-inducible factor-1alpha (HIF-1alpha)-prolyl-4-hydroxylase-2, stabilizes HIF-1alpha expression, and normalizes immature vasculature in db/db mice
    Jian xiong Chen
    Department of Pediatrics, Division of Neonatology, Vanderbilt University Medical Center, Nashville, TN, USA
    Diabetes 57:3335-43. 2008
    ..We investigated the potential roles and intracellular mechanisms of angiopoietin-1 (Ang-1) gene therapy on myocardial HIF-1alpha stabilization and vascular maturation in db/db mice...
  22. ncbi The androgen receptor is significantly associated with vascular endothelial growth factor and hypoxia sensing via hypoxia-inducible factors HIF-1a, HIF-2a, and the prolyl hydroxylases in human prostate cancer
    Jane L Boddy
    Harold Hopkins Department of Urology, Royal Berkshire Hospital, Reading, UK
    Clin Cancer Res 11:7658-63. 2005
    ..The study aimed to assess whether a relationship exists in human prostate cancer between expression of the androgen receptor, HIFs, and the key angiogenesis factor, vascular endothelial growth factor (VEGF)...
  23. ncbi Differential and reciprocal regulation between hypoxia-inducible factor-alpha subunits and their prolyl hydroxylases in pulmonary arteries of rat with hypoxia-induced hypertension
    Yun Rong Chen
    Department of Respiratory Medicine, Hunan Institute of Gerontology, Hunan Province Geriatric Hospital, Changsha 410001, China
    Acta Biochim Biophys Sin (Shanghai) 38:423-34. 2006
    ..through post-translational hydroxylation by their three prolyl hydroxylase domain-containing proteins (PHD1, PHD2 and PHD3). PHDs could also be regulated by HIF...
  24. ncbi Selective inhibition of hypoxia-inducible factor (HIF) prolyl-hydroxylase 1 mediates neuroprotection against normoxic oxidative death via HIF- and CREB-independent pathways
    Ambreena Siddiq
    Department of Neurosciences, Burke Medical Research Institute, White Plains, New York 10605, USA
    J Neurosci 29:8828-38. 2009
    ..Finally, RNA interference to PHD1 but not isoforms PHD2 or PHD3 prevents oxidative death, independent of HIF activation...
  25. ncbi Kinetic characterization and identification of a novel inhibitor of hypoxia-inducible factor prolyl hydroxylase 2 using a time-resolved fluorescence resonance energy transfer-based assay technology
    Jennifer H Dao
    Amgen Inc, One Amgen Center Drive, HTS Molecular Pharmacology, Thousand Oaks, CA 91320 1789, USA
    Anal Biochem 384:213-23. 2009
    ..Here we report the enzymatic characterization of full-length recombinant human HIF-PHD2 using a novel and sensitive catalytic assay...
  26. ncbi Caloric restriction counteracts age-dependent changes in prolyl-4-hydroxylase domain (PHD) 3 expression
    Susanne Rohrbach
    Institute of Pathophysiology, Martin Luther University Halle Wittenberg, Ernst Grube Str 40, 06112 Halle, Germany
    Biogerontology 9:169-76. 2008
    ..In the present study we demonstrate that elevated PHD3, but not PHD1 or PHD2, expression is not restricted to the heart but does also occur in rat skeletal muscle and liver...
  27. ncbi Role of N-acetyl-N-nitroso-tryptophan as nitric oxide donor in the modulation of HIF-1-dependent signaling
    Utta Berchner-Pfannschmidt
    Institut fur Physiologie, Universitat Duisburg Essen, Germany
    Biol Chem 391:533-40. 2010
    ..HIF-1 degradation is controlled by prolyl hydroxylase 2 (PHD2) which needs to be inhibited for HIF-1 accumulation...
  28. ncbi Gallate, the component of HIF-inducing catechins, inhibits HIF prolyl hydroxylase
    Fuyo Tsukiyama
    Department of Thoracic and Cardiovascular Surgery, Osaka Medical College, Daigakumachi, Takatsuki 569 8686, Japan
    Biochem Biophys Res Commun 351:234-9. 2006
    ..Model building studies on the human HIF prolyl hydroxylase 2 showed that the two phenolate oxygen atoms of gallate form a chelate with the active site Fe(2+), while ..
  29. ncbi Expression and actions of HIF prolyl-4-hydroxylase in the rat kidneys
    Ningjun Li
    Dept of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth Univ, PO Box 980613, Richmond, VA 23298, USA
    Am J Physiol Renal Physiol 292:F207-16. 2007
    ..RT-PCR, Western blot, and immunohistochemical analyses, we have demonstrated that all three isoforms of PHD, PHD1, PHD2, and PHD3, are expressed in the kidneys and that PHD2 is the most abundant isoform...
  30. ncbi Hypoxia-inducible factor prolyl-hydroxylase 2 senses high-salt intake to increase hypoxia inducible factor 1alpha levels in the renal medulla
    Zhengchao Wang
    Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, PO Box 980613, Richmond, VA 23298, USA
    Hypertension 55:1129-36. 2010
    ..b>PHD2 is the predominant isoform of PHDs in the kidney and is primarily expressed in the renal medulla...
  31. ncbi Enhancement of angiogenesis through stabilization of hypoxia-inducible factor-1 by silencing prolyl hydroxylase domain-2 gene
    Shourong Wu
    Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
    Mol Ther 16:1227-34. 2008
    ..Prolyl hydroxylase domain-2 (PHD2) protein induces the degradation of HIF-1 by hydroxylating specific prolyl residues...
  32. ncbi Rapid degradation of hypoxia-inducible factor-1alpha by KRH102053, a new activator of prolyl hydroxylase 2
    H J Choi
    Department of Dental Pharmacology, School of Dentistry, Chonbuk National University, Jeon Ju, Republic of Korea
    Br J Pharmacol 154:114-25. 2008
    ..Although PHD2 plays a key role in regulating the levels of HIF, chemical activators of PHD2 are relatively unknown...
  33. ncbi Inhibition of prolyl hydroxylase domain proteins promotes therapeutic revascularization
    Céline Loinard
    Paris Cardiovascular Research Center, INSERM U970, Hopital Europeen Georges Pompidou, Universite Paris 5, Paris, France
    Circulation 120:50-9. 2009
    ..factor (HIF) subunits are destabilized via the O(2)-dependent prolyl hydroxylase domain proteins (PHD1, PHD2, and PHD3)...
  34. ncbi Short hairpin RNA interference therapy for ischemic heart disease
    Mei Huang
    Stanford University School of Medicine, Edwards Building R354, Stanford, CA 94305 5344, USA
    Circulation 118:S226-33. 2008
    ..However, hypoxia inducible factor-1 alpha is naturally degraded by prolyl hydroxylase-2 (PHD2) protein...
  35. ncbi Inhibition of hypoxia-inducible factor-targeting prolyl hydroxylase domain-containing protein 2 (PHD2) enhances matrix synthesis by human chondrocytes
    Brendan L Thoms
    From The Kennedy Institute of Rheumatology, Faculty of Medicine, Imperial College London, 65 Aspenlea Road, London W6 8LH, United Kingdom
    J Biol Chem 285:20472-80. 2010
    ..Here, we have identified PHD2 as the dominant isoenzyme regulating HIF-2alpha stability in human chondrocytes...
  36. ncbi Src activates HIF-1? not through direct phosphorylation of HIF-1? specific prolyl-4 hydroxylase 2 but through activation of the NADPH oxidase/Rac pathway
    Ho Youl Lee
    Department of Life Science, University of Seoul, Siripdae gil 13, Dongdaemun Gu, Seoul, Korea
    Carcinogenesis 32:703-12. 2011
    ..normoxic condition, the HIF-1? subunit is hydroxylated by its specific prolyl-4 hydroxylase 2, given the acronym PHD2. Hydroxylated HIF-1? becomes a target for von Hippel-Lindau (VHL), which functions as an E3 ubiquitin ligase...
  37. ncbi Essential role for prolyl hydroxylase domain protein 2 in oxygen homeostasis of the adult vascular system
    Kotaro Takeda
    Center for Vascular Biology, Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06030 3501, USA
    Circulation 116:774-81. 2007
    Prolyl hydroxylase domain (PHD) proteins, including PHD1, PHD2, and PHD3, mediate oxygen-dependent degradation of hypoxia-inducible factor (HIF)-alpha subunits...
  38. ncbi Increased prolyl 4-hydroxylase domain proteins compensate for decreased oxygen levels. Evidence for an autoregulatory oxygen-sensing system
    Daniel P Stiehl
    Institute of Physiology and Center for Integrative Human Physiology, University of Zurich, CH 8057 Zurich, Switzerland
    J Biol Chem 281:23482-91. 2006
    ..Paradoxically, the expression of two family members (PHD2 and PHD3) is induced in hypoxic cell culture despite the reduced availability of the oxygen co-substrate, and it ..
  39. ncbi Prolyl hydroxylase domain (PHD) 2 affects cell migration and F-actin formation via RhoA/rho-associated kinase-dependent cofilin phosphorylation
    Sabine Vogel
    Department of Cardiovascular Physiology, Universitatsmedizin Gottingen, Georg August University Gottingen, D 37073 Gottingen, Germany
    J Biol Chem 285:33756-63. 2010
    ..To gain further insight into PHD function, we generated knockdown cell models for the PHD2 isoform, which is the main isoform regulating HIF-1? hydroxylation and thus stability in normoxia...
  40. ncbi Hypoxia-inducible factor prolyl-hydroxylase: purification and assays of PHD2
    Kirsty S Hewitson
    Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford, United Kingdom
    Methods Enzymol 435:25-42. 2007
    ..This chapter details methods for the purification and assaying of PHD2, the most abundant PHD and the most important in setting steady-state levels of HIF-alpha...
  41. ncbi Somatic inactivation of the PHD2 prolyl hydroxylase causes polycythemia and congestive heart failure
    Yoji Andrew Minamishima
    Department of Medical Oncology, Brigham and Women s Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Blood 111:3236-44. 2008
    ..PHD1, PHD2, and PHD3) capable of catalyzing this reaction have been identified, although PHD2 (also called Egln1) appears to be the primary HIF prolyl hydroxylase in cell culture experiments...
  42. ncbi Prolyl hydroxylase domain protein 2 (PHD2) mediates oxygen-induced retinopathy in neonatal mice
    Li Juan Duan
    Center for Vascular Biology, Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06030 3501, USA
    Am J Pathol 178:1881-90. 2011
    ..Here we show that prolyl hydroxylase domain protein 2 (PHD2), an enzyme mostly responsible for oxygen-induced degradation of HIF-? proteins, plays a major role in oxygen-..
  43. ncbi Prolyl-4-hydroxylase PHD2- and hypoxia-inducible factor 2-dependent regulation of amphiregulin contributes to breast tumorigenesis
    M R Bordoli
    Institute of Physiology and Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
    Oncogene 30:548-60. 2011
    ..and bad prognosis, the function of the HIF-? protein stability regulating prolyl-4-hydroxylase domain enzyme PHD2 in carcinogenesis is less well understood...
  44. ncbi Prolyl hydroxylase-3 is down-regulated in colorectal cancer cells and inhibits IKKbeta independent of hydroxylase activity
    Jing Xue
    Key Laboratory of Nutrition and Metabolisms, Institute of Nutritional Sciences, SIBS, Chinese Academy of Sciences, Shanghai, China
    Gastroenterology 138:606-15. 2010
    ..The PHD family comprises PHD1, PHD2, and PHD3...
  45. ncbi The prolyl-hydroxylase EGLN3 and not EGLN1 is inactivated by methylation in plasma cell neoplasia
    Eleftheria Hatzimichael
    Department of Haematology, University of Ioannina, Greece
    Eur J Haematol 84:47-51. 2010
    b>EGLN1 and EGLN3 are members of the egg-laying-defective 9 (EglN) prolyl-hydroxylases which during normoxia catalyse hydroxylation of the hypoxia-inducible factor (HIF)-1alpha, thereby promoting its ubiquitination by a complex containing ..
  46. ncbi A feedback loop involving the Phd3 prolyl hydroxylase tunes the mammalian hypoxic response in vivo
    Yoji Andrew Minamishima
    Department of Medical Oncology, Dana Farber Cancer Institute and Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell Biol 29:5729-41. 2009
    ..Among the three Phd family members, Phd2 appears to be the primary HIF prolyl hydroxylase...
  47. ncbi Hypoxic preconditioning produces differential expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and its regulatory enzyme HIF prolyl hydroxylase 2 in neonatal rat brain
    Nicole M Jones
    Brain Injury and Repair Program, Howard Florey Institute, The University of Melbourne, Parkville, Vic, Australia
    Neurosci Lett 404:72-7. 2006
    ....
  48. ncbi Characterization of different isoforms of the HIF prolyl hydroxylase PHD1 generated by alternative initiation
    Ya Min Tian
    Oxygen Sensing Group, The Henry Wellcome Building for Molecular Physiology, University of Oxford, Roosevelt Drive, Headington, Oxford OX3 7BN, UK
    Biochem J 397:179-86. 2006
    ..Three oxygen-dependent prolyl hydroxylase enzymes [PHD1 (prolyl hydroxylase domain 1), PHD2 and PHD3] control the abundance of HIF...
  49. ncbi Hypoxia-inducible factor 1 (HIF-1) pathway
    Gregg L Semenza
    Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Broadway Research Building, Suite 671, 733 North Broadway, Baltimore, MD 21205, USA
    Sci STKE 2007:cm8. 2007
    ..by O2-dependent hydroxylation of proline residue 402, 564, or both, by prolyl hydroxylase domain protein 2 (PHD2), which promotes binding of the von Hippel-Lindau protein (VHL), leading to ubiquitination and proteasomal ..
  50. ncbi Melanoma antigen-11 inhibits the hypoxia-inducible factor prolyl hydroxylase 2 and activates hypoxic response
    Olga Aprelikova
    Laboratory of Tumor and Stem Cell Biology, National Cancer Institute, Bethesda, Maryland 20892, USA
    Cancer Res 69:616-24. 2009
    ..between melanoma antigen-11 (MAGE-11) cancer-testis antigen and the major HIF-alpha hydroxylating enzyme PHD2. The interaction was confirmed by a pull-down assay, coimmunoprecipitation, and colocalization in both normoxic and ..
  51. ncbi Effects of prolyl hydroxylase inhibitors on adipogenesis and hypoxia inducible factor 1 alpha levels under normoxic conditions
    Z Elizabeth Floyd
    Stem Cell Laboratory and Clinical Nutrition Research Unit, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana 70808, USA
    J Cell Biochem 101:1545-57. 2007
    ..hydroxylase domain 1 (PHD1) isoform of the HIF prolyl hydroxylases is expressed in early adipogenesis and the PHD2 and PHD3 isoforms are expressed during late adipogenesis...
  52. ncbi Mutation analysis of HIF prolyl hydroxylases (PHD/EGLN) in individuals with features of phaeochromocytoma and renal cell carcinoma susceptibility
    Dewi Astuti
    Centre for Rare Diseases and Personalised Medicine, University of Birmingham, Birmingham B15 2TT, UK
    Endocr Relat Cancer 18:73-83. 2011
    ..The 2-oxoglutarate-dependent prolyl hydroxylase enzymes PHD1 (EGLN2), PHD2 (EGLN1) and PHD3 (EGLN3) have a key role in regulating the stability of HIF-? subunits (and hence expression of the HIF-? ..
  53. ncbi Identification and characterization of the hypoxia-responsive element in human stanniocalcin-1 gene
    A Y S Law
    Department of Biology, Hong Kong Baptist University, Kowloon Tong, Hong Kong, Hong Kong
    Mol Cell Endocrinol 314:118-27. 2010
    ..the stability of HIF-1 alpha protein by overexpressing HIF-1 alpha or the silencing of prolyl hydroxylase-2 (PHD2), to illustrate HIF-1 activation of STC1 promoter-driven luciferase activity...
  54. ncbi DNA methylation analysis of the HIF-1? prolyl hydroxylase domain genes PHD1, PHD2, PHD3 and the factor inhibiting HIF gene FIH in invasive breast carcinomas
    Katie T Huang
    Department of Pathology, Molecular Pathology Research and Development Laboratory, Peter MacCallum Cancer Centre, Melbourne, Vic, Australia
    Histopathology 57:451-60. 2010
    Hypoxia-inducible factor-1 (HIF-1) activity is regulated by prolyl hydroxylase (PHD1, PHD2, PHD3) and factor inhibiting HIF-1 (FIH) that target the ? subunit of HIF-1 (HIF-1?) for proteosomal degradation...
  55. ncbi Cardiomyocyte-specific prolyl-4-hydroxylase domain 2 knock out protects from acute myocardial ischemic injury
    Marion Hölscher
    Department of Cardiovascular Physiology, Universitatsmedizin Gottingen, Georg August University Gottingen, Gottingen, Germany
    J Biol Chem 286:11185-94. 2011
    ..We have disrupted PHD2 in cardiomyocytes (cPhd (-/-)) using Phd2(flox/flox) mice in combination with MLCvCre mice, which resulted in HIF-1?..
  56. ncbi The key hypoxia regulated gene CAIX is upregulated in basal-like breast tumours and is associated with resistance to chemotherapy
    E Y Tan
    Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Oxford, UK
    Br J Cancer 100:405-11. 2009
    ..tumours from 188 patients were stained for hypoxia-inducible factor (HIF)-1alpha, prolyl hydroxylase (PHD)1, PHD2, PHD3 and factor inhibiting HIF (FIH)-1, and carbonic anhydrase (CA) IX stained in 456 breast tumours...
  57. ncbi Hypoxia-induced assembly of prolyl hydroxylase PHD3 into complexes: implications for its activity and susceptibility for degradation by the E3 ligase Siah2
    Koh Nakayama
    Signal Transduction Program, Burnham Institute for Medical Research, La Jolla, CA 92037, USA
    Biochem J 401:217-26. 2007
    ..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...
  58. ncbi Role and regulation of prolyl hydroxylase domain proteins
    G H Fong
    Center for Vascular Biology, Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06030 3501, USA
    Cell Death Differ 15:635-41. 2008
    ..Interestingly, while PHDs regulate HIF-alpha protein stability, PHD2 and PHD3 themselves are subject to feedback upregulation by HIFs...
  59. ncbi Erythrocytosis-associated HIF-2alpha mutations demonstrate a critical role for residues C-terminal to the hydroxylacceptor proline
    Paul W Furlow
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 284:9050-8. 2009
    ..However, each exhibits a distinct profile with respect to their effects on PHD2 binding and von Hippel Lindau interaction...
  60. ncbi Regulation of adult erythropoiesis by prolyl hydroxylase domain proteins
    Kotaro Takeda
    Center for Vascular Biology, Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06030 3501, USA
    Blood 111:3229-35. 2008
    ..HIF-2alpha, which is known to activate Epo expression, accumulated in the liver. In adult mice deficient for PHD2, the prototypic Epo transcriptional activator HIF-1alpha accumulated in both the kidney and liver...
  61. ncbi Prolyl-hydroxylase inhibition and HIF activation in osteoblasts promotes an adipocytic phenotype
    R Irwin
    Department of Physiology, Biomedical Imaging Research Center, Michigan State University, East Lansing, MI 48824, USA
    J Cell Biochem 100:762-72. 2007
    ..We also demonstrate that prolyl-hydroxylases 2 and 3 (PHD2, PHD3), one of the major factors coordinating HIF degradation under normoxic but not hypoxic conditions, are ..
  62. ncbi Hypoxia-inducible factor-1? contributes to the profibrotic action of angiotensin II in renal medullary interstitial cells
    Zhengchao Wang
    Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298, USA
    Kidney Int 79:300-10. 2011
    ..Overexpression of a prolyl-hydroxylase domain-containing protein 2 (PHD2) transgene, the predominant renal HIF prolyl-hydroxylase, attenuated the effects of angiotensin II and its gene ..
  63. ncbi Novel drugs and the response to hypoxia: HIF stabilizers and prolyl hydroxylase
    Masaomi Nangaku
    Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7 3 1, Hongo, Bunkyo ku, Tokyo 113 8655, Japan
    Recent Pat Cardiovasc Drug Discov 1:129-39. 2006
    ..the mammalian genome encodes three closely related proteins that have HIF prolyl hydroxylase activity, PHD1, PHD2 and PHD3...
  64. ncbi An oxygen molecular sensor, the HIF prolyl 4-hydroxylase, in the marine protist Perkinsus olseni
    Ricardo B Leite
    CCMar University of Algarve, Campus de Gambelas, Faro 8005 139, Portugal
    Protist 159:355-68. 2008
    ..it was also possible to conclude, through phylogenetic analysis, that Perkinsus HPH is closer to the actual HPH2 from mammals, thus providing additional evidence supporting previous data pointing to HPH2 as the most ancestral of ..
  65. ncbi Characterization of low-molecular-weight antiyeast metabolites produced by a food-protective Lactobacillus-Propionibacterium coculture
    Susanne Miescher Schwenninger
    Laboratory of Food Biotechnology, Institute of Food Science and Nutrition, ETH Zentrum, 8092 Zurich, Switzerland
    J Food Prot 71:2481-7. 2008
    ..paracasei SM20 and Propionibacterium jensenii SM11 in supplemented whey permeate medium yielding cell-free supernatants with high ..
  66. ncbi Nitric oxide donor, (+/-)-S-nitroso-N-acetylpenicillamine, stabilizes transactive hypoxia-inducible factor-1alpha by inhibiting von Hippel-Lindau recruitment and asparagine hydroxylation
    Young Kwon Park
    Department of Life Science, University of Seoul, Seoul, Korea
    Mol Pharmacol 74:236-45. 2008
    ..peptides by measuring the activities of the corresponding enzymes, HIF-1alpha-specific proline hydroxylase 2 (PHD2) and the HIF-1alpha-specific asparagine hydroxylase, designated factor inhibiting HIF-1alpha (FIH-1), respectively...
  67. ncbi Inhibition of poly adenosine diphosphate-ribose polymerase decreases hepatocellular carcinoma growth by modulation of tumor-related gene expression
    Rosa Quiles-Perez
    San Cecilio University Hospital, Granada, Spain
    Hepatology 51:255-66. 2010
    ..growth factor receptor-1, VEGFR1], epidermal growth factor receptor [EPAS1]/hypoxia-inducible factor 2 [HIF2A], EGLN1 [PHD2], epidermal growth factor receptor [EGFR], MYC, JUND, SPP1 [OPN], hepatocyte growth factor [HGF]) was found ..
  68. ncbi Genetics of pheochromocytomas and paragangliomas
    Giuseppe Opocher
    Veneto Institute of Oncology, Padova, Italy
    Best Pract Res Clin Endocrinol Metab 24:943-56. 2010
    ..More rarely, two other genes may predispose to pheochromocytoma/paraganglioma development: KIF1Bbeta and PHD2. A mechanism conducing to a defective apoptosis is the common pathways of those genes...
  69. ncbi Nutritional evaluation of high-digestible sorghum for pigs and broiler chicks
    E K D Nyannor
    Department of Animal Science, Purdue University, West Lafayette, IN 47907 2054, USA
    J Anim Sci 85:196-203. 2007
    ..were conducted to evaluate the nutritional quality of 2 varieties of Purdue high-digestible sorghum (PHD1 and PHD2) and a normal sorghum, compared with corn, in diets of pigs and broiler chicks. In Exp...
  70. ncbi Hph1p and Hph2p, novel components of calcineurin-mediated stress responses in Saccharomyces cerevisiae
    Victoria L Heath
    Department of Biological Sciences, Stanford University, Stanford, CA 94305 5020, USA
    Eukaryot Cell 3:695-704. 2004
    ..We have identified Hph1p as a novel substrate of calcineurin. HPH1 (YOR324C) and its homolog HPH2 (YAL028W) encode tail-anchored integral membrane proteins that interact with each other in the yeast two-hybrid ..
  71. ncbi The involvement of hypoxia-inducible transcription factor-1-dependent pathway in nickel carcinogenesis
    Konstantin Salnikow
    The Nelson Institute of Environmental Medicine, National Institute of Environmental Health Sciences Center, National Institutes of Health and The New York University Cancer Institute, School of Medicine, New York, NY 10016, USA
    Cancer Res 63:3524-30. 2003
    ..hypoxia-inducible genes up-regulated by nickel in a HIF-dependent manner including BCL-2-binding protein Nip3, EGLN1, hypoxia-inducible gene 1 (HIG1), and prolyl 4-hydroxylase...
  72. ncbi Enzyme substrate recognition in oxygen sensing: how the HIF trap snaps
    Eric Metzen
    Institute of Physiology, University of Lubeck, Ratzeburger Allee 160, D23538 Lübeck, Federal Republic of Germany
    Biochem J 408:e5-6. 2007
    ..PHD1/EGLN2 and PHD2/EGLN1 hydroxylate both ODDs with higher activity towards CODD, whereas PHD3/EGLN3 is specific for CODD...
  73. ncbi A candidate mouse model for Hartnup disorder deficient in neutral amino acid transport
    D J Symula
    McArdle Laboratory for Cancer Research, University of Wisconsin, Madison 53706, USA
    Mamm Genome 8:102-7. 1997
    The mutant mouse strain HPH2 (hyperphenylalaninemia) was isolated after N-ethyl-N-nitrosourea (ENU) mutagenesis on the basis of delayed plasma clearance of an injected load of phenylalanine...
  74. ncbi Short-term treatment with L-arginine prevents the smoking-induced impairment of endothelial function and vascular elastic properties in young individuals
    Gerasimos Siasos
    Athens University Medical School, 1st Cardiology Department, Greece
    Int J Cardiol 126:394-9. 2008
    ..Aim of the present study was to investigate in healthy smokers the effect of a short-term daily L-arginine administration on vascular function...
  75. ncbi Double immunohistochemical staining method for HIF-1alpha and its regulators PHD2 and PHD3 in formalin-fixed paraffin-embedded tissues
    Mary M Vaughan
    Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
    Appl Immunohistochem Mol Morphol 18:375-81. 2010
    ..Another human, poorly differentiated SCC xenograft, FaDu, without hypoxic areas, was used as a negative control. PHD2 and 3 immunostaining was optimized individually using the human kidney...
  76. ncbi Binding of the CHD4 PHD2 finger to histone H3 is modulated by covalent modifications
    Catherine A Musselman
    Department of Pharmacology, School of Medicine, University of Colorado Denver, Aurora, CO 80045, USA
    Biochem J 423:179-87. 2009
    ..CHD4 contains two PHD (plant homeodomain) fingers of unknown function. Here we show that the second PHD finger (PHD2) of CHD4 recognizes the N-terminus of histone H3 and that this interaction is facilitated by acetylation or ..
  77. ncbi Hph1 and Hph2 are novel components of the Sec63/Sec62 posttranslational translocation complex that aid in vacuolar proton ATPase biogenesis
    Francisco J Piña
    Department of Biology, 371 Serra Drive, Stanford University, Stanford, CA 94305 5020, USA
    Eukaryot Cell 10:63-71. 2011
    Hph1 and Hph2 are homologous integral endoplasmic reticulum (ER) membrane proteins required for Saccharomyces cerevisiae survival under environmental stress conditions...
  78. ncbi The von Hippel Lindau/hypoxia-inducible factor (HIF) pathway regulates the transcription of the HIF-proline hydroxylase genes in response to low oxygen
    Luis del Peso
    Departamento de Bioquimica, Facultad de Medicina, Universidad Autonoma de Madrid, Arzobispo Morcillo s n, 28029 Madrid, Spain
    J Biol Chem 278:48690-5. 2003
    ..Here we show that the induction of EGLN1 and -3 by hypoxia is found in a wide range of cell types...
  79. ncbi Prolyl hydroxylase 3 interacts with Bcl-2 to regulate doxorubicin-induced apoptosis in H9c2 cells
    Ying Liu
    Key Laboratory of Arrhythmias, Ministry of Education, East Hospital, Tongji University School of Medicine, 200120 Shanghai, China
    Biochem Biophys Res Commun 401:231-7. 2010
    ..Three PHD isoforms (PHD1, PHD2 and PHD3) have been identified in mammalian cells...
  80. ncbi Studies on the reaction of nitric oxide with the hypoxia-inducible factor prolyl hydroxylase domain 2 (EGLN1)
    Rasheduzzaman Chowdhury
    Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK
    J Mol Biol 410:268-79. 2011
    ..and biophysical studies on the reaction of prolyl hydroxylase domain-containing enzyme (PHD) isoform 2 (EGLN1) with nitric oxide and a nitric oxide transfer reagent...
  81. ncbi 'ome on the Range: altitude adaptation, positive selection, and himalayan genomics
    Martin J Macinnis
    University of British Columbia, School of Kinesiology, Vancouver, British Columbia, Canada
    High Alt Med Biol 12:133-9. 2011
    ..The results were exciting, intriguing, and controversial. Several genes, most notably EGLN1 and EPAS1, were identified as strong candidates for a role in evolutionary adaptation to high altitude, and the ..
  82. ncbi The prolyl hydroxylase enzymes are positively associated with hypoxia-inducible factor-1? and vascular endothelial growth factor in human breast cancer and alter in response to primary systemic treatment with epirubicin and tamoxifen
    Stephen B Fox
    Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria 3002, Australia
    Breast Cancer Res 13:R16. 2011
    ..the relationship of expression of hypoxia inducible factor (HIF)-1?-modifying enzymes prolyl hydroxylase (PHD)1, PHD2 and PHD3 to response of tumours and survival in breast cancer patients enrolled in a phase II trial of neoadjuvant ..
  83. ncbi Expression of the cellular oxygen sensor PHD2 (EGLN-1) predicts radiation sensitivity in squamous cell cancer of the head and neck
    Marjaana Luukkaa
    Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland
    Int J Radiat Biol 85:900-8. 2009
    ..b>PHD2 (Prolyl hydroxylase domain protein 2) isoform is the main regulator of HIF-1alpha degradation in normoxia and mild ..
  84. ncbi Molecular evolution of the metazoan PHD-HIF oxygen-sensing system
    Kalle T Rytkönen
    Division of Genetics and Physiology, Department of Biology, University of Turku, Turku, Finland
    Mol Biol Evol 28:1913-26. 2011
    ..HIF-2 alpha N-terminal ODD domain, together with a functional divergence associated with the known differences in PHD2 versus PHD1/3 substrate specificity, have contributed to the tighter oxygen-sensitive regulation of HIF-1 alpha ..
  85. ncbi Integrity of the prolyl hydroxylase domain protein 2:erythropoietin pathway in aging mice
    Xiping Li
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Blood Cells Mol Dis 45:9-19. 2010
    ..Recent studies have identified PHD2 as the critical PHD isoform regulating the EPO gene...
  86. ncbi Major vault protein forms complexes with hypoxia-inducible factor (HIF)-1alpha and reduces HIF-1alpha level in ACHN human renal adenocarcinoma cells
    Ken Ichi Iwashita
    Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
    Cancer Sci 101:920-6. 2010
    ..the ubiquitination and degradation of HIF-1alpha protein; and (iii) vaults form complexes with HIF-1alpha, PHD2, and pVHL...
  87. ncbi Vitamin C is dispensable for oxygen sensing in vivo
    Katarzyna J Nytko
    Institute of Physiology and Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
    Blood 117:5485-93. 2011
    ..A Cys201Ser mutation in PHD2 increased basal hydroxylation rates and conferred resistance to oxidative damage in vitro, suggesting that this ..
  88. ncbi Relationship among circulating hemoglobin, nitric oxide synthase activities and angiogenic poise in red- and white-blooded Antarctic notothenioid fishes
    Jody M Beers
    School of Marine Sciences, University of Maine, 5751 Murray Hall, Orono, Maine 04469 5751, USA
    Comp Biochem Physiol A Mol Integr Physiol 156:422-9. 2010
    ..aceratus (Hb-) and G. gibberifrons (Hb+), respectively]. Levels of mRNA for hypoxia-induced (HIF-1alpha and PHD2) and angiogenic genes (VEGF) were similar in red- and white-blooded species, indicating that vascular maintenance ..
  89. ncbi Biochemical characterization of human HIF hydroxylases using HIF protein substrates that contain all three hydroxylation sites
    Melissa B Pappalardi
    Department of Cancer Research, GlaxoSmithKline, Collegeville, PA 19426, USA
    Biochem J 436:363-9. 2011
    ..ketoglutarate)-dependent prolyl hydroxylase enzymes [PHD (prolyl hydroxylase domain) isoenzymes 1-3 or PHD1, PHD2 and PHD3] and one asparaginyl hydroxylase [FIH (factor inhibiting HIF)]...
  90. ncbi Apicidin upregulates PHD2 prolyl hydroxylase gene expression in cervical cancer cells
    Marta Durczak
    Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Poznan, Poland
    Anticancer Drugs 21:619-24. 2010
    It was recently reported that the reduced expression of hypoxia-inducible factor prolyl 4-hydroxylase PHD2 inhuman cancers correlates with increased angiogenesis...
  91. ncbi Increased chemoresistance induced by inhibition of HIF-prolyl-hydroxylase domain enzymes
    Nils Brökers
    Department of Cardiovascular Physiology, Georg August University Gottingen, Gottingen, Germany
    Cancer Sci 101:129-36. 2010
    ..which develops as a consequence of inhibiting the PHD activity, was further supported in a tetracycline-inducible PHD2 knockdown HeLa cell model...
  92. ncbi Lactate influx through the endothelial cell monocarboxylate transporter MCT1 supports an NF-?B/IL-8 pathway that drives tumor angiogenesis
    Frederique Vegran
    Universite Catholique de Louvain, Pole of Pharmacology and Therapeutics UCL FATH, Angiogenesis and Cancer Research Laboratory, Institute of Experimental and Clinical Research IREC, Brussels, Belgium
    Cancer Res 71:2550-60. 2011
    ..b>PHD2 silencing in endothelial cells recapitulated the proangiogenic effects of lactate, whereas a blocking IL-8 antibody ..
  93. ncbi Toxoplasma gondii activates hypoxia-inducible factor (HIF) by stabilizing the HIF-1alpha subunit via type I activin-like receptor kinase receptor signaling
    Mandi Wiley
    Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA
    J Biol Chem 285:26852-60. 2010
    ..Infection significantly decreases PHD2 abundance, which is the key prolyl hydroxylase for regulating HIF-1alpha...
  94. ncbi Carbon monoxide promotes VEGF expression by increasing HIF-1alpha protein level via two distinct mechanisms, translational activation and stabilization of HIF-1alpha protein
    Yoon Kyung Choi
    Vascular System Research Center and Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Kangwon Do 200 701, Republic of Korea
    J Biol Chem 285:32116-25. 2010
    ..These results suggest that CO stimulates VEGF production by increasing HIF-1? protein level via two distinct mechanisms, translational stimulation and protein stabilization of HIF-1?...
  95. ncbi Ascorbic acid regulates osterix expression in osteoblasts by activation of prolyl hydroxylase and ubiquitination-mediated proteosomal degradation pathway
    Weirong Xing
    Musculoskeletal Disease Center, Jerry L Pettis VA Medical Center, California, USA
    Physiol Genomics 43:749-57. 2011
    ..Knockdown of PHD2 expression by Lentivirus-mediated shRNA abolished AA-induced Osx induction and alkaline phosphatase activity...
  96. ncbi Genetic mapping of hph2, a mutation affecting amino acid transport in the mouse
    D J Symula
    McArdle Laboratory for Cancer Research, University of Wisconsin, Madison 53706, USA
    Mamm Genome 8:98-101. 1997
    We describe the genetic mapping of hyperphenylal-aninemia 2 (hph2), a recessive mutation in the mouse that causes deficient amino acid transport similar to Hartnup disorder, a human genetic amino acid transport disorder...
  97. ncbi AKAP12 regulates human blood-retinal barrier formation by downregulation of hypoxia-inducible factor-1alpha
    Yoon Kyung Choi
    NeuroVascular Coordination Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151 742, Korea
    J Neurosci 27:4472-81. 2007
    ..protein by enhancing the interaction of HIF-1alpha with pVHL (von Hippel-Lindau tumor suppressor protein) and PHD2 (prolyl hydroxylase 2)...
  98. ncbi Hypoxia-inducible factors in the first trimester human lung
    Frederick Groenman
    Canadian Institute of Health Research Group in Lung Development, Hospital for Sick Children Research Institute, Department of Pediatrics, University of Toronto, Toronto, ON, Canada
    J Histochem Cytochem 55:355-63. 2007
    ..Immunoreactivity for PHD1, PHD3, and seven in absentia homolog (SIAH)1 was noted in the pulmonary epithelium. PHD2 was not expressed in the airway epithelium, but in the lung parenchyma...
  99. ncbi Prolyl hydroxylase domain 2 protein suppresses hypoxia-induced endothelial cell proliferation
    Kotaro Takeda
    Center for Vascular Biology, University of Connecticut Health Center, 263 Farmington Ave, Farmington, CT 06030 3501, USA
    Hypertension 49:178-84. 2007
    Prolyl hydroxylase domain 2 protein (PHD2) signals the degradation of hypoxia-inducible factor (HIF)-1alpha by hydroxylating specific prolyl residues located within oxygen-dependent degradation domains...
  100. ncbi Factors affecting human IgE and IgG responses to allergen-like Schistosoma mansoni antigens: Molecular structure and patterns of in vivo exposure
    Colin M Fitzsimmons
    Department of Pathology, University of Cambridge, Cambridge, UK
    Int Arch Allergy Immunol 142:40-50. 2007
    ..Here we compare human IgE and IgG responses to other family members, Sm20.8 and Sm21.7, as well as to SmDLC1, relating these to antigen structure and expression in parasite life stages.
  101. ncbi A novel series of imidazo[1,2-a]pyridine derivatives as HIF-1alpha prolyl hydroxylase inhibitors
    Namal C Warshakoon
    Procter and Gamble Pharmaceuticals, Inc, 8700 Mason Montgomery Road, Mason, OH 45040, USA
    Bioorg Med Chem Lett 16:5598-601. 2006
    Utilizing modeling information from a recently resolved structure of human HIF-1alpha prolyl hydroxylase (EGLN1) and structure-based design, a novel series of imidazo[1,2-a]pyridine derivatives was prepared...

Research Grants85

  1. Mechanisms of Hyperbaric Oxygen Induced Brain Protection
    John H Zhang; Fiscal Year: 2010
    ..HBO-PC produces moderate levels of reactive oxygen species (ROS) which, by destabilization of prolyl hydroxylase 2 (PHD2), induces HIF-1 accumulation in brain tissue...
  2. Molecular Imaging of Targeted Cardiac Gene Therapy
    Joseph C Wu; Fiscal Year: 2010
    ..However, HIF-11 has a short biological half-life due to endogenous degradation by prolyl hydroxylase-2 (PHD2)...
  3. Regulation of the cullin family E3 ubiquitin ligases
    Zhen Qiang Pan; Fiscal Year: 2007
    ..Hydroxylation of HIF-10_ at proline residue 564, by the PHO1/SM20 family prolyl hydroxylase, is required for its interaction with pVHL to initiate the ubiquitination...
  4. Regulation of the cullin family E3 ubiquitin ligases
    Zhen Qiang Pan; Fiscal Year: 2006
    ..Hydroxylation of HIF-1alpha at proline residue 564, by the PHO1/SM20 family prolyl hydroxylase, is required for its interaction with pVHL to initiate the ubiquitination...
  5. Regulation of vascular maturation/regression in diabetes
    Jian xiong Chen; Fiscal Year: 2010
    ..Our laboratory has shown a sustained increase in angiopoietin-2 (Ang-2) and prolyl hydroxylase-2 (PHD2) expression, and reduced Ang-1/Tie-2 and HIF- 11/apelin expression in diabetic mice...
  6. Functional Analysis of the Von Hippel-Lindau Protein
    William G Kaelin; Fiscal Year: 2010
    ..physical interaction of pVHL with HIFalpha requires that HIFalpha be hydroxylated on one of two prolyl residues by EglN1, which is an oxygen-dependent enzyme...
  7. Functional Analysis of the Von Hippel-Lindau Protein
    William Kaelin; Fiscal Year: 2009
    ..physical interaction of pVHL with HIFalpha requires that HIFalpha be hydroxylated on one of two prolyl residues by EglN1, which is an oxygen-dependent enzyme...
  8. Functional Analysis of the Von Hippel-Lindau Protein
    William Kaelin; Fiscal Year: 2009
    ..physical interaction of pVHL with HIFalpha requires that HIFalpha be hydroxylated on one of two prolyl residues by EglN1, which is an oxygen-dependent enzyme...
  9. Functional Analysis of the Von Hippel-Lindau Protein
    William Kaelin; Fiscal Year: 2007
    ..physical interaction of pVHL with HIFalpha requires that HIFalpha be hydroxylated on one of two prolyl residues by EglN1, which is an oxygen-dependent enzyme...
  10. Molecular Mechanisms of the Hypoxic Response
    Frank S Lee; Fiscal Year: 2010
    ..There are three HIF-( isoforms (HIF-1(, HIF-2(, and HIF-3() and three Prolyl Hydroxylase Domain proteins (PHD1, PHD2, PHD3) that can hydroxylate them, raising the critical question of which isoforms are important for human ..
  11. A Novel Regulator of Oxygen Homeostasis
    Frank Lee; Fiscal Year: 2007
    ..PHD consist of three isoforms, and current evidence indicates that PHD2 is the key PHD isoform responsible for maintaining HIF at essentially undetectable levels under normoxia...
  12. A Novel Regulator of Oxygen Homeostasis
    Frank Lee; Fiscal Year: 2009
    ..PHD consist of three isoforms, and current evidence indicates that PHD2 is the key PHD isoform responsible for the maintaining HIF at essentially undetectable levels under normoxia...
  13. Renal medullary HIF prolyl hydroxylases and salt sensitivity of blood pressure
    Ningjun Li; Fiscal Year: 2009
    ..We will also determine whether stimulation of PHD activity and overexpression of PHD2 gene to block HIF-1 a mediated gene expression in the renal medulla increases the salt sensitivity of arterial ..
  14. Renal medullary HIF prolyl hydroxylases and salt sensitivity of blood pressure
    Ningjun Li; Fiscal Year: 2010
    ..We will also determine whether stimulation of PHD activity and overexpression of PHD2 gene to block HIF-1 a mediated gene expression in the renal medulla increases the salt sensitivity of arterial ..
  15. GROWTH RELATED GENES IN VASCULAR SMOOTH MUSCLE
    MARK TAUBMAN; Fiscal Year: 2003
    ..b>SM20 is developmentally regulated in the heart, arterial wall, and skeletal muscle and is induced during differentiation ..
  16. The Novel Oncogene Jcf1 in Development and Oncogenesis
    Philip Tsichlis; Fiscal Year: 2007
    ..The protein encoded by this gene is 1336 amino acids long, contains a jumonji (JmjC) domain, a CXXC/PHD2 zinc finger domain, an F box and a leucine rich repeat (LRR) and is localized in the nucleus...
  17. GROWTH RELATED GENES IN VASCULAR SMOOTH MUSCLE
    MARK TAUBMAN; Fiscal Year: 1999
    ..A recently developed antibody to SM20 will be used to determine the intra- and extra- cellular distribution of SM-20 protein in rat and human VSMC and ..
  18. The role of Ndy1 in epigenetic gene silencing and stem cell biology
    Philip N Tsichlis; Fiscal Year: 2010
    ..chromatin-associated histone H3 demethylase, which contains an N-termal JmjC domain, a CXXC zinc finger domain, a PHD2 zinc finger, an F-box, and a leucine-rich repeat (LRR) and is expressed most highly in stem cells, such as ..
  19. Hypoxia-Inducible Factor 1 and Oxygen Homeostasis
    Gregg Semenza; Fiscal Year: 2009
    ....
  20. HIF-1-Regulated Endothelial Progenitor Cell Recruitment in Burn Wound Healing
    Gregg Semenza; Fiscal Year: 2007
    ..abstract_text> ..
  21. HIF-1-Regulated Endothelial Progenitor Cell Recruitment in Burn Wound Healing
    Gregg Semenza; Fiscal Year: 2007
    ....
  22. EXPRESSION OF HUMAN ERYTHROPOIETIN GENE
    Gregg Semenza; Fiscal Year: 1993
    ..EPO gene DNA from affected family members will be amplified by the polymerase chain reaction and analyzed by nucleotide sequence determination to identify potential disease-causing mutations...
  23. EXPRESSION OF HUMAN ERYTHROPOIETIN GENE
    Gregg Semenza; Fiscal Year: 2002
    ..abstract_text> ..
  24. HYPOXIA INDUCIBLE FACTOR I AND OXYGEN HOMEOSTASIS
    Gregg Semenza; Fiscal Year: 2004
    ..The knowledge gained from the proposed experiments will be relevant to the treatment of many clinical conditions in which hypoxia or ischemia plays an important pathophysiologic role. ..
  25. HYPOXIA INDUCIBLE FACTOR 1 AND OXYGEN HOMEOSTASIS
    Gregg Semenza; Fiscal Year: 1999
    ....
  26. POSTTRANSCRIPTIONAL REGULATION--CATECHOLAMINE SYNTHESIS
    MARIA CZYZYK KRZESKA; Fiscal Year: 2000
    ..Such system is necessary to study THE mRNA stability regulation without non- specific transcription blockers and will facilitate future studies of mRNA stability in the transgenic animals. ..
  27. Regulation of Cell Function by Intermittent Hypoxia
    MARIA CZYZYK KRZESKA; Fiscal Year: 2007
    ..3) We will determine the role of proline hydroxylation in Rpb1 ubiquitination by VHL and measure the effects of IH and oxidative stress on proline hydroxylation in brain extracts from exposed animals, and in PC12 cells. ..