Peter J Ratcliffe

Summary

Affiliation: University of Oxford
Country: UK

Publications

  1. pmc Oxygen sensing and hypoxia signalling pathways in animals: the implications of physiology for cancer
    Peter J Ratcliffe
    Henry Wellcome Building for Molecular Physiology, Old Road Campus, University of Oxford, Oxford OX3 7BN, UK
    J Physiol 591:2027-42. 2013
  2. ncbi Understanding hypoxia signalling in cells--a new therapeutic opportunity?
    Peter J Ratcliffe
    University of Oxford
    Clin Med 6:573-8. 2006
  3. pmc HIF-1 and HIF-2: working alone or together in hypoxia?
    Peter J Ratcliffe
    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    J Clin Invest 117:862-5. 2007
  4. ncbi Fumarate hydratase deficiency and cancer: activation of hypoxia signaling?
    Peter J Ratcliffe
    The Henry Wellcome Building for Molecular Physiology, University of Oxford, Headington Campus, Roosevelt Drive, Oxford OX3 7BN, United Kingdom
    Cancer Cell 11:303-5. 2007
  5. ncbi From erythropoietin to oxygen: hypoxia-inducible factor hydroxylases and the hypoxia signal pathway
    Peter J Ratcliffe
    Renal and Cell Physiology Group, The Henry Wellcome Building of Genomic Medicine, University of Oxford, UK
    Blood Purif 20:445-50. 2002
  6. ncbi Determination and comparison of specific activity of the HIF-prolyl hydroxylases
    Jason R Tuckerman
    Henry Wellcome Building for Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN, UK
    FEBS Lett 576:145-50. 2004
  7. ncbi Genetic analysis of the role of the asparaginyl hydroxylase factor inhibiting hypoxia-inducible factor (FIH) in regulating hypoxia-inducible factor (HIF) transcriptional target genes [corrected]
    Ineke P Stolze
    The Henry Wellcome Building of Genomic Medicine, University of Oxford, Roosevelt Drive, Headington, Oxford OX3 7BN
    J Biol Chem 279:42719-25. 2004
  8. pmc Contrasting properties of hypoxia-inducible factor 1 (HIF-1) and HIF-2 in von Hippel-Lindau-associated renal cell carcinoma
    Raju R Raval
    The Henry Wellcome Building for Molecular Physiology, University of Oxford, Oxford OX3 7BN, United Kingdom
    Mol Cell Biol 25:5675-86. 2005
  9. doi MYPT1, the targeting subunit of smooth-muscle myosin phosphatase, is a substrate for the asparaginyl hydroxylase factor inhibiting hypoxia-inducible factor (FIH)
    James D Webb
    Nuffield Department of Clinical Medicine, University of Oxford, Headington, UK
    Biochem J 420:327-33. 2009
  10. 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

Detail Information

Publications95

  1. pmc Oxygen sensing and hypoxia signalling pathways in animals: the implications of physiology for cancer
    Peter J Ratcliffe
    Henry Wellcome Building for Molecular Physiology, Old Road Campus, University of Oxford, Oxford OX3 7BN, UK
    J Physiol 591:2027-42. 2013
    ..The relationship of these cellular signalling pathways to the integrated physiology of oxygen homeostasis and the implication of dysregulating these massive physiological pathways in diseases such as cancer are discussed...
  2. ncbi Understanding hypoxia signalling in cells--a new therapeutic opportunity?
    Peter J Ratcliffe
    University of Oxford
    Clin Med 6:573-8. 2006
    ..This paper will review these developments and consider the biological and potential therapeutic implications...
  3. pmc HIF-1 and HIF-2: working alone or together in hypoxia?
    Peter J Ratcliffe
    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    J Clin Invest 117:862-5. 2007
    ..These results demonstrate distinct functions for different HIF-alpha isoforms that could potentially be exploited in therapeutic approaches to anemia...
  4. ncbi Fumarate hydratase deficiency and cancer: activation of hypoxia signaling?
    Peter J Ratcliffe
    The Henry Wellcome Building for Molecular Physiology, University of Oxford, Headington Campus, Roosevelt Drive, Oxford OX3 7BN, United Kingdom
    Cancer Cell 11:303-5. 2007
    ....
  5. ncbi From erythropoietin to oxygen: hypoxia-inducible factor hydroxylases and the hypoxia signal pathway
    Peter J Ratcliffe
    Renal and Cell Physiology Group, The Henry Wellcome Building of Genomic Medicine, University of Oxford, UK
    Blood Purif 20:445-50. 2002
    ....
  6. ncbi Determination and comparison of specific activity of the HIF-prolyl hydroxylases
    Jason R Tuckerman
    Henry Wellcome Building for Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN, UK
    FEBS Lett 576:145-50. 2004
    ....
  7. ncbi Genetic analysis of the role of the asparaginyl hydroxylase factor inhibiting hypoxia-inducible factor (FIH) in regulating hypoxia-inducible factor (HIF) transcriptional target genes [corrected]
    Ineke P Stolze
    The Henry Wellcome Building of Genomic Medicine, University of Oxford, Roosevelt Drive, Headington, Oxford OX3 7BN
    J Biol Chem 279:42719-25. 2004
    ....
  8. pmc Contrasting properties of hypoxia-inducible factor 1 (HIF-1) and HIF-2 in von Hippel-Lindau-associated renal cell carcinoma
    Raju R Raval
    The Henry Wellcome Building for Molecular Physiology, University of Oxford, Oxford OX3 7BN, United Kingdom
    Mol Cell Biol 25:5675-86. 2005
    ..These findings indicate that therapeutic approaches to targeting of the HIF system, at least in this setting, will need to take account of HIF isoform-specific functions...
  9. doi MYPT1, the targeting subunit of smooth-muscle myosin phosphatase, is a substrate for the asparaginyl hydroxylase factor inhibiting hypoxia-inducible factor (FIH)
    James D Webb
    Nuffield Department of Clinical Medicine, University of Oxford, Headington, UK
    Biochem J 420:327-33. 2009
    ..These results extend the range of FIH substrates and suggest that cross-competition between ARDs and HIF-CAD, and between ARDs themselves, may be extensive and have important effects on hypoxia signalling...
  10. 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
    ....
  11. doi Regulation of Jumonji-domain-containing histone demethylases by hypoxia-inducible factor (HIF)-1alpha
    Patrick J Pollard
    Henry Wellcome Building for Molecular Physiology, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
    Biochem J 416:387-94. 2008
    ..Given the importance of histone methylation status in defining patterns of gene expression under different physiological and pathophysiological conditions, these findings predict a role for the HIF system in epigenetic regulation...
  12. ncbi The HIF prolyl hydroxylase PHD3 is a potential substrate of the TRiC chaperonin
    Norma Masson
    The Henry Wellcome Building of Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN, UK
    FEBS Lett 570:166-70. 2004
    ..The cytosolic chaperonin TRiC was found to copurify with PHD3 in extracts from several cell types. Our results indicate that PHD3 is a TRiC substrate, providing another step at which PHD3 activity may be regulated...
  13. ncbi Interaction of hydroxylated collagen IV with the von hippel-lindau tumor suppressor
    Alexandra Grosfeld
    Henry Wellcome Building for Molecular Physiology, University of Oxford, Oxford OX3 7BN, United Kingdom
    J Biol Chem 282:13264-9. 2007
    ..The interaction was suppressed by a wide range of tumor-associated mutations, including those that do not disturb the regulation of HIF, supporting a role in HIF-independent tumor suppressor functions...
  14. pmc Factor-inhibiting hypoxia-inducible factor (FIH) catalyses the post-translational hydroxylation of histidinyl residues within ankyrin repeat domains
    Ming Yang
    Oxford Centre for Integrative Systems Biology, University of Oxford, Oxford, UK
    FEBS J 278:1086-97. 2011
    ..NMR and crystallographic analyses show that the histidinyl hydroxylation occurs at the β-position. The results further expand the scope of FIH-catalysed hydroxylations...
  15. doi Regulation of growth differentiation factor 15 expression by intracellular iron
    Samira Lakhal
    Henry Wellcome Building for Molecular Physiology, University of Oxford, Oxford, UK
    Blood 113:1555-63. 2009
    ..These findings indicate that GDF15 can be induced by pathophysiologic changes in iron availability, raising important questions about the mechanism of regulation and its role in iron homeostasis...
  16. pmc Proteomics-based identification of novel factor inhibiting hypoxia-inducible factor (FIH) substrates indicates widespread asparaginyl hydroxylation of ankyrin repeat domain-containing proteins
    Matthew E Cockman
    Central Proteomics Facility, University of Oxford, Oxford, United Kingdom
    Mol Cell Proteomics 8:535-46. 2009
    ..These findings indicate that asparaginyl hydroxylation is likely to be widespread among the approximately 300 ARD-containing species in the human proteome...
  17. ncbi Asparaginyl hydroxylation of the Notch ankyrin repeat domain by factor inhibiting hypoxia-inducible factor
    Mathew L Coleman
    Henry Wellcome Building for Molecular Physiology, University of Oxford, Oxford, OX3 7BN, United Kingdom
    J Biol Chem 282:24027-38. 2007
    ..We propose that ARD proteins function as natural inhibitors of FIH and that the hydroxylation status of these proteins provides another oxygen-dependent interface that modulates HIF signaling...
  18. pmc A role for cytosolic fumarate hydratase in urea cycle metabolism and renal neoplasia
    Julie Adam
    Cancer Biology and Metabolism Group, Nuffield Department of Medicine, Henry Wellcome Building for Molecular Physiology, University of Oxford, Oxford OX3 7BN, UK
    Cell Rep 3:1440-8. 2013
    ..Our findings highlight the importance of extramitochondrial metabolic pathways in FH-associated oncogenesis and the urea cycle/arginine metabolism as a potential therapeutic target...
  19. pmc The FIH hydroxylase is a cellular peroxide sensor that modulates HIF transcriptional activity
    Norma Masson
    Henry Wellcome Building for Molecular Physiology, University of Oxford, Oxford OX3 7BN, UK
    EMBO Rep 13:251-7. 2012
    ..These contrasting sensitivities indicate that oxidant stress is unlikely to signal hypoxia directly to the HIF system, but that hypoxia and oxidant stress can interact functionally as distinct regulators of HIF transcriptional output...
  20. pmc Renal cyst formation in Fh1-deficient mice is independent of the Hif/Phd pathway: roles for fumarate in KEAP1 succination and Nrf2 signaling
    Julie Adam
    Nuffield Department of Medicine, Henry Wellcome Building for Molecular Physiology, University of Oxford, Oxford OX3 7BN, UK
    Cancer Cell 20:524-37. 2011
    ....
  21. pmc Asparagine and aspartate hydroxylation of the cytoskeletal ankyrin family is catalyzed by factor-inhibiting hypoxia-inducible factor
    Ming Yang
    Chemistry Research Laboratory and Oxford Centre for Integrative Systems Biology, University of Oxford, Oxford OX1 3TA, United Kingdom
    J Biol Chem 286:7648-60. 2011
    ....
  22. pmc 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
    ..The data define the existence of a further level of control in the pathway that regulates cellular responses to hypoxia...
  23. doi Dual-action inhibitors of HIF prolyl hydroxylases that induce binding of a second iron ion
    Kar Kheng Yeoh
    Chemistry Research Laboratory, Department of Chemistry, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, UK
    Org Biomol Chem 11:732-45. 2013
    ..Some compounds were shown to inhibit the HIF hydroxylases in human hepatoma and renal carcinoma cell lines...
  24. doi Oxygenase-catalyzed ribosome hydroxylation occurs in prokaryotes and humans
    Wei Ge
    Chemistry Research Laboratory and Oxford Centre for Integrative Systems Biology, University of Oxford, Oxford, UK
    Nat Chem Biol 8:960-2. 2012
    ..This work reveals new therapeutic possibilities via oxygenase inhibition and by targeting modified over unmodified ribosomes...
  25. pmc Cardiopulmonary function in two human disorders of the hypoxia-inducible factor (HIF) pathway: von Hippel-Lindau disease and HIF-2alpha gain-of-function mutation
    Federico Formenti
    Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Rd, Oxford, OX1 3PT, UK
    FASEB J 25:2001-11. 2011
    ....
  26. pmc Quantitative mass spectrometry reveals dynamics of factor-inhibiting hypoxia-inducible factor-catalyzed hydroxylation
    Rachelle S Singleton
    Center for Cellular and Molecular Physiology, University of Oxford, Oxford OX3 7BN, United Kingdom
    J Biol Chem 286:33784-94. 2011
    ..These findings suggest that asparaginyl hydroxylation of HIF-1 and ARD proteins is regulated by oxygen over a similar range, potentially tuning the HIF transcriptional response through competition between the two types of substrate...
  27. pmc Genome-wide association of hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha DNA binding with expression profiling of hypoxia-inducible transcripts
    David R Mole
    Henry Wellcome Building of Molecular Physiology, University of Oxford, Oxford OX3 7BN, United Kingdom
    J Biol Chem 284:16767-75. 2009
    ..Given emerging evidence for biologically distinct functions of HIF-1alpha versus HIF-2alpha understanding the mechanisms restricting HIF-2alpha activity will be of interest...
  28. pmc Human AlkB homologue 5 is a nuclear 2-oxoglutarate dependent oxygenase and a direct target of hypoxia-inducible factor 1α (HIF-1α)
    Armin Thalhammer
    Chemistry Research Laboratory and the Oxford Centre for Integrative Systems Biology, Department of Chemistry, University of Oxford, Oxford, United Kingdom
    PLoS ONE 6:e16210. 2011
    ..Our findings define a new class of HIF-transcriptional target gene and suggest that ALKBH5 may have a role in the regulation of cellular responses to hypoxia...
  29. doi Asparagine beta-hydroxylation stabilizes the ankyrin repeat domain fold
    Leanne Kelly
    The Chemistry Research Laboratory and Oxford Centre for Integrative Systems Biology, University of Oxford, Oxford, UKOX1 3TA
    Mol Biosyst 5:52-8. 2009
    ..We propose that intracellular protein hydroxylation is much more common than previously thought and that one of its roles is stabilization of localized regions of ARD folds...
  30. ncbi The prolyl hydroxylase enzymes that act as oxygen sensors regulating destruction of hypoxia-inducible factor alpha
    Carsten Willam
    Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK
    Adv Enzyme Regul 44:75-92. 2004
  31. pmc Regulation of type II transmembrane serine proteinase TMPRSS6 by hypoxia-inducible factors: new link between hypoxia signaling and iron homeostasis
    Samira Lakhal
    Henry Wellcome Building for Molecular Physiology, University of Oxford, Oxford OX3 7BN, United Kingdom
    J Biol Chem 286:4090-7. 2011
    ..Our results reveal a potential role for TMPRSS6 in hepcidin regulation by hypoxia and provide a new molecular link between oxygen sensing and iron homeostasis...
  32. ncbi 2-oxoglutarate analogue inhibitors of HIF prolyl hydroxylase
    David R Mole
    Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK
    Bioorg Med Chem Lett 13:2677-80. 2003
    ..Various analogues of the 2-oxoglutarate cosubstrate were synthesised and shown to inhibit the activity of human hypoxia-inducible factor-1alpha prolyl hydroxylases in cell-free extracts...
  33. ncbi Regulation of the HIF pathway: enzymatic hydroxylation of a conserved prolyl residue in hypoxia-inducible factor alpha subunits governs capture by the pVHL E3 ubiquitin ligase complex
    David R Mole
    Henry Wellcome Building for Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN, UK
    Adv Enzyme Regul 42:333-47. 2002
  34. pmc Peptide blockade of HIFalpha degradation modulates cellular metabolism and angiogenesis
    Carsten Willam
    Henry Wellcome Building for Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN, United Kingdom
    Proc Natl Acad Sci U S A 99:10423-8. 2002
    ..These results demonstrate the feasibility of using these polypeptides to enhance HIF activity, opening additional therapeutic avenues for ischemic diseases...
  35. ncbi HIF prolyl hydroxylases in the rat; organ distribution and changes in expression following hypoxia and coronary artery ligation
    Carsten Willam
    Henry Wellcome Building for Molecular Physiology, Oxford, UK
    J Mol Cell Cardiol 41:68-77. 2006
    ..Inducibility of PHD2 and 3 by hypoxia and ischemia in vivo has important implications both for the pathophysiology of conditions where oxygen supply is deranged and for attempts to manipulate the HIF system therapeutically...
  36. pmc Studies on the activity of the hypoxia-inducible-factor hydroxylases using an oxygen consumption assay
    Dominic Ehrismann
    Chemistry Research Laboratory, Department of Chemistry and Oxford Centre for Molecular Sciences, University of Oxford, Oxford OXI 3TA, UK
    Biochem J 401:227-34. 2007
    ....
  37. pmc Differential sensitivity of hypoxia inducible factor hydroxylation sites to hypoxia and hydroxylase inhibitors
    Ya Min Tian
    Nuffield Department of Clinical Medicine, Henry Wellcome Building for Molecular Physiology, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, United Kingdom
    J Biol Chem 286:13041-51. 2011
    ....
  38. pmc Posttranslational hydroxylation of ankyrin repeats in IkappaB proteins by the hypoxia-inducible factor (HIF) asparaginyl hydroxylase, factor inhibiting HIF (FIH)
    Matthew E Cockman
    Henry Wellcome Building for Molecular Physiology, University of Oxford, Oxford OX3 7BN, United Kingdom
    Proc Natl Acad Sci U S A 103:14767-72. 2006
    ....
  39. ncbi HIF prolyl and asparaginyl hydroxylases in the biological response to intracellular O(2) levels
    Norma Masson
    The Henry Wellcome Building of Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN, UK
    J Cell Sci 116:3041-9. 2003
    ..The involvement of at least two distinct types of 2-OG-dependent oxygenase in oxygen-regulated transcription suggests that these enzymes may be well suited to a role in cellular oxygen sensing...
  40. ncbi Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1 alpha
    Jonathan M Elkins
    Oxford Centre for Molecular Sciences and the Dyson Perrins Laboratory, University of Oxford, South Parks Road, Oxford OX1 3QY, United Kingdom
    J Biol Chem 278:1802-6. 2003
    ..Conserved structural motifs within FIH imply it is one of an extended family of Fe((II)) oxygenases involved in gene regulation...
  41. 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
    ..Assays are described that measure the activity of PHD2 via direct and indirect means. Furthermore, conditions for the screening of small molecules against PHD2 are described...
  42. ncbi Regulation of angiogenesis by hypoxia: role of the HIF system
    Christopher W Pugh
    The Henry Wellcome Building of Genomic Medicine, Roosevelt Drive, Oxford, OX3 7BN, UK
    Nat Med 9:677-84. 2003
    ..We also discuss the implications of oncogenic activation of extensive, physiologically interconnected hypoxia pathways for the tumor phenotype...
  43. pmc The increase in pulmonary arterial pressure caused by hypoxia depends on iron status
    Thomas G Smith
    Department of Physiology, Anatomy and Genetics, University of Oxford, Sherrington Building, Parks Road, Oxford OX1 3PT, UK
    J Physiol 586:5999-6005. 2008
    ..Further research should investigate the potential for therapeutic manipulation of iron status in the management of hypoxic pulmonary hypertensive disease...
  44. pmc Mutation of von Hippel-Lindau tumour suppressor and human cardiopulmonary physiology
    Thomas G Smith
    Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, United Kingdom
    PLoS Med 3:e290. 2006
    ..This study investigated patients with Chuvash polycythaemia in order to analyse the role of the VHL-HIF pathway in systemic human cardiopulmonary physiology...
  45. pmc The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases
    Rasheduzzaman Chowdhury
    Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK
    EMBO Rep 12:463-9. 2011
    ....
  46. ncbi Concordant regulation of gene expression by hypoxia and 2-oxoglutarate-dependent dioxygenase inhibition: the role of HIF-1alpha, HIF-2alpha, and other pathways
    Gareth P Elvidge
    Oxygen Sensing Group, The Henry Wellcome Building for Molecular Physiology, University of Oxford, Oxford OX3 7BN
    J Biol Chem 281:15215-26. 2006
    ..Nevertheless, the definition of genes regulated by both hypoxia and DMOG, but not HIF, distinguished other pathways most likely involving the action of 2-OG-dependent dioxygenases on non-HIF substrates...
  47. pmc Roles of individual prolyl-4-hydroxylase isoforms in the first 24 hours following transient focal cerebral ischaemia: insights from genetically modified mice
    Ruo Li Chen
    Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Headley Way, Headington, Oxford, OX3 9DU, UK
    J Physiol 590:4079-91. 2012
    ..These need to be considered in optimizing therapeutic effects of PHD inhibitors, particularly when isoform specific inhibitors become available...
  48. pmc Common genetic variants at the 11q13.3 renal cancer susceptibility locus influence binding of HIF to an enhancer of cyclin D1 expression
    Johannes Schödel
    Henry Wellcome Building for Molecular Physiology, University of Oxford, Oxford, UK
    Nat Genet 44:420-5, S1-2. 2012
    ..The protective haplotype impairs binding of HIF-2, resulting in an allelic imbalance in cyclin D1 expression, thus affecting a link between hypoxia pathways and cell cycle control...
  49. ncbi Dynamic combinatorial chemistry employing boronic acids/boronate esters leads to potent oxygenase inhibitors
    Marina Demetriades
    Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA UK
    Angew Chem Int Ed Engl 51:6672-5. 2012
    ..This dynamic combinatorial mass spectrometry technique could potentially be applied to the identification of other protein inhibitors...
  50. ncbi Structural basis for the recognition of hydroxyproline in HIF-1 alpha by pVHL
    Wai Ching Hon
    Division of Structural Biology, Henry Wellcome Building of Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN, UK
    Nature 417:975-8. 2002
    ..This mechanism provides a new focus for development of therapeutic agents to modulate cellular responses to hypoxia...
  51. pmc Regulation of human metabolism by hypoxia-inducible factor
    Federico Formenti
    Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom
    Proc Natl Acad Sci U S A 107:12722-7. 2010
    ..These findings have significant implications for the development of therapeutic approaches targeting the HIF pathway...
  52. doi FIH-dependent asparaginyl hydroxylation of ankyrin repeat domain-containing proteins
    Matthew E Cockman
    Henry Wellcome Building for Molecular Physiology, University of Oxford, Oxford, United Kingdom
    Ann N Y Acad Sci 1177:9-18. 2009
    ....
  53. ncbi Analysis of von Hippel-Lindau tumor suppressor as a mediator of cellular oxygen sensing
    Norma Masson
    The Henry Wellcome Building of Genomic Medicine, University of Oxford, United Kingdom
    Methods Enzymol 381:305-20. 2004
  54. doi A photoreactive small-molecule probe for 2-oxoglutarate oxygenases
    Dante Rotili
    Department of Chemistry and the Oxford Centre for Integrative Systems Biology, Chemistry Research Laboratory, University of Oxford, UK
    Chem Biol 18:642-54. 2011
    ..The results also suggest that small-molecule probes may be suitable for substrate identification studies...
  55. doi PHF8, a gene associated with cleft lip/palate and mental retardation, encodes for an Nepsilon-dimethyl lysine demethylase
    Christoph Loenarz
    Oxford Centre for Integrative Systems Biology, University of Oxford, Oxford, UK
    Hum Mol Genet 19:217-22. 2010
    ..Our results will enable further studies aimed at defining the molecular links between developmental changes in histone methylation status, congenital disorders and MR...
  56. pmc High-resolution genome-wide mapping of HIF-binding sites by ChIP-seq
    Johannes Schödel
    Henry Wellcome Building for Molecular Physiology, University of Oxford, Oxford, UK
    Blood 117:e207-17. 2011
    ....
  57. pmc Dysregulation of hypoxia pathways in fumarate hydratase-deficient cells is independent of defective mitochondrial metabolism
    Linda O'Flaherty
    Henry Wellcome Building for Molecular Physiology, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
    Hum Mol Genet 19:3844-51. 2010
    ..The findings indicate that upregulation of HIF-1alpha arises from competitive inhibition of the 2-OG-dependent HIF hydroxylases by fumarate and not from disruption of mitochondrial energy metabolism...
  58. ncbi Normoxic stabilization of hypoxia-inducible factor-1alpha by modulation of the labile iron pool in differentiating U937 macrophages: effect of natural resistance-associated macrophage protein 1
    Helen J Knowles
    Cancer Research UK Molecular Oncology Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK
    Cancer Res 66:2600-7. 2006
    ..These results indicate that physiologic changes in macrophage iron metabolism have an important effect on HIF hydroxylase pathways and suggest means by which the system could be manipulated for therapeutic benefit...
  59. doi Extensive regulation of the non-coding transcriptome by hypoxia: role of HIF in releasing paused RNApol2
    Hani Choudhry
    The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
    EMBO Rep 15:70-6. 2014
    ..These findings indicate that the transcriptional response to hypoxia is substantially more extensive than previously considered. ..
  60. ncbi HIF activation identifies early lesions in VHL kidneys: evidence for site-specific tumor suppressor function in the nephron
    Stefano J Mandriota
    Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, United Kingdom
    Cancer Cell 1:459-68. 2002
    ..In proximal tubules these were almost entirely unicellular, whereas multicellular foci were almost exclusively seen in the distal nephron...
  61. pmc Carotid body hyperplasia and enhanced ventilatory responses to hypoxia in mice with heterozygous deficiency of PHD2
    Tammie Bishop
    Wellcome Trust Centre for Human Genetics, Roosevelt Drive, University of Oxford, Oxford OX3 7BN, UK
    J Physiol 591:3565-77. 2013
    ....
  62. pmc Genetic analysis of pathways regulated by the von Hippel-Lindau tumor suppressor in Caenorhabditis elegans
    Tammie Bishop
    The Henry Wellcome Building of Genomic Medicine, University of Oxford, Oxford, United Kingdom
    PLoS Biol 2:e289. 2004
    ....
  63. doi Photoactivable peptides for identifying enzyme-substrate and protein-protein interactions
    Dante Rotili
    University of Oxford, Department of Chemistry and the Oxford Centre for Integrative Systems Biology, Chemistry Research Laboratory, Mansfield Road, Oxford, OX1 3TA, United Kingdom
    Chem Commun (Camb) 47:1488-90. 2011
    ..Photoactivated cross-linking of peptides to proteins is a useful strategy for identifying enzyme-substrate and protein-protein interactions in cell lysates as demonstrated by studies on the human hypoxia inducible factor system...
  64. ncbi Cellular oxygen sensing in health and disease
    David R Mole
    University of Oxford, Headington Campus, Roosevelt Drive, Oxford, UK
    Pediatr Nephrol 23:681-94. 2008
    ....
  65. doi Aberrant succination of proteins in fumarate hydratase-deficient mice and HLRCC patients is a robust biomarker of mutation status
    Chiara Bardella
    Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, Oxford, UK
    J Pathol 225:4-11. 2011
    ..The investigation of whether metabolites in other tumour types produce protein modification signature(s) that can be assayed using similar strategies will be of interest in future studies of cancer...
  66. ncbi Oxygen sensors and angiogenesis
    Patrick H Maxwell
    Henry Wellcome Building of Genomic Medicine, University of Oxford, Roosevelt Drive, OX3 7BN, UK
    Semin Cell Dev Biol 13:29-37. 2002
    ..The HIF prolyl hydroxylases (PHD enzymes) act as oxygen sensors regulating HIF, and hence angiogenesis. The PHD-HIF-VHL system provides a range of opportunities for therapeutic manipulation...
  67. ncbi Oxygen sensing and hypoxia-induced responses
    Mathew L Coleman
    Henry Wellcome Building for Molecular Physiology, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, U K
    Essays Biochem 43:1-15. 2007
    ....
  68. pmc The hypoxia-inducible transcription factor pathway regulates oxygen sensing in the simplest animal, Trichoplax adhaerens
    Christoph Loenarz
    Chemistry Research Laboratory and the Oxford Centre for Integrative Systems Biology, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK
    EMBO Rep 12:63-70. 2011
    ..Cross-genomic analyses rationalize the relative importance of HIF system components, and imply that the HIF system is likely to be present in all animals, but is unique to this kingdom...
  69. pmc The human side of hypoxia-inducible factor
    Thomas G Smith
    Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK
    Br J Haematol 141:325-34. 2008
    ..This article reviews our current understanding of the importance of HIF in human systems-level physiology, and is modelled around the classic physiological response to high-altitude hypoxia...
  70. ncbi First United Kingdom Heart and Renal Protection (UK-HARP-I) study: biochemical efficacy and safety of simvastatin and safety of low-dose aspirin in chronic kidney disease
    Colin Baigent
    Clinical Trial Service Unit, Oxford University, Oxford, UK
    Am J Kidney Dis 45:473-84. 2005
    ..Patients with chronic kidney disease are at increased risk for cardiovascular disease, but the efficacy and safety of simvastatin and aspirin are unknown in this patient group...
  71. ncbi Regulation of HIF: prolyl hydroxylases
    Ineke P Stolze
    Henry Wellcome Building for Molecular Physiology, Roosevelt Drive, Oxford OX3 7BN, UK
    Novartis Found Symp 272:15-25; discussion 25-36. 2006
    ....
  72. pmc Abnormal sympathoadrenal development and systemic hypotension in PHD3-/- mice
    Tammie Bishop
    The Henry Wellcome Building for Molecular Physiology, University of Oxford, Headington Campus, Roosevelt Drive, Oxford OX3 7BN, United Kingdom
    Mol Cell Biol 28:3386-400. 2008
    ..Perturbation of this interface between developmental and adaptive signaling by hypoxic, metabolic, or other stresses could have important effects on key sympathoadrenal functions, such as blood pressure regulation...
  73. pmc Novel Insights into FH-associated Disease are KEAPing the Lid on Oncogenic HIF Signalling
    Julie Adam
    The Nuffield Department of Medicine, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK
    Oncotarget 2:820-1. 2011
    ..Given the resurgence of interest in the metabolic switch associated with cancer cells proposed many years ago by Warburg, HLRCC affords a new paradigm to investigate the importance of alterations in cellular metabolism and cancer...
  74. pmc Control of the hypoxic response in Drosophila melanogaster by the basic helix-loop-helix PAS protein similar
    Sofía Lavista-Llanos
    Instituto de Investigaciones Bioquimicas Fundacion Campomar, Buenos Aires 1405, Argentina
    Mol Cell Biol 22:6842-53. 2002
    ..Tight conservation of the HIF/prolyl hydroxylase system in Drosophila provides a new focus for understanding oxygen homeostasis in intact multicellular organisms...
  75. doi Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway
    William G Kaelin
    Howard Hughes Medical Institute, Boston, MA 02115, USA
    Mol Cell 30:393-402. 2008
    ..HIF affects signaling pathways that influence development, metabolism, inflammation, and integrative physiology. Accordingly, HIF-modulatory drugs are now being developed for diverse diseases...
  76. ncbi Expression of hypoxia-inducible factors in human renal cancer: relationship to angiogenesis and to the von Hippel-Lindau gene mutation
    Kevin J Turner
    Imperial Cancer Research Fund Molecular Oncology Laboratory and Angiogenesis Group, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DU, UK
    Cancer Res 62:2957-61. 2002
    ..These results suggest that activation of the HIF pathway is functionally important in CC-RCC development and might provide a new therapeutic target...
  77. ncbi Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural family
    Kirsty S Hewitson
    Oxford Centre for Molecular Sciences, Dyson Perrins Laboratory, South Parks Road, Oxford OX1 3QY, United Kingdom
    J Biol Chem 277:26351-5. 2002
    ....
  78. ncbi Expression of hypoxia-inducible factor-1alpha and -2alpha in hypoxic and ischemic rat kidneys
    Christian Rosenberger
    Department of Nephrology and Medical Intensive Care, Charite, Campus Virchow Klinikum, Humboldt University, Augustenburger Platz 1, 13353 Berlin, Germany
    J Am Soc Nephrol 13:1721-32. 2002
    ..The expression of HIF-2alpha in peritubular fibroblasts suggests a role in erythropoietin regulation...
  79. ncbi Widespread hypoxia-inducible expression of HIF-2alpha in distinct cell populations of different organs
    Michael S Wiesener
    Department of Nephrology and Medical Intensive Care, Charite, Humboldt University Berlin, Germany
    FASEB J 17:271-3. 2003
    ..These data indicate that HIF-2 plays an important role in the transcriptional response to hypoxia in vivo, which is not confined to the vasculature and is complementary to rather than redundant with HIF-1...
  80. ncbi New insights into an enigmatic tumour suppressor
    Peter J Ratcliffe
    Nat Cell Biol 5:7-8. 2003
  81. ncbi Analogues of dealanylalahopcin are inhibitors of human HIF prolyl hydroxylases
    Imre Schlemminger
    Oxford Centre for Molecular Sciences, Dyson Perrins Laboratory, South Parks Road, UK
    Bioorg Med Chem Lett 13:1451-4. 2003
    ..Analogues of the naturally occurring cyclic hydroxamate dealanylalahopcin, which is an inhibitor of procollagen prolyl-4-hydroxylase, were synthesised and shown to be inhibitors of the human hypoxia-inducible factor prolyl hydroxylases...
  82. ncbi Effect of ascorbate on the activity of hypoxia-inducible factor in cancer cells
    Helen J Knowles
    Cancer Research United Kingdom Molecular Oncology Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS
    Cancer Res 63:1764-8. 2003
    ..These results indicate that both ascorbate and iron availability have major effects on HIF, and imply that the system is commonly regulated by limiting hydroxylase activity under normoxic tissue culture conditions...
  83. ncbi ExCITED about HIF
    Shoumo Bhattacharya
    Nat Struct Biol 10:501-3. 2003
  84. ncbi Predominant role of hypoxia-inducible transcription factor (Hif)-1alpha versus Hif-2alpha in regulation of the transcriptional response to hypoxia
    Heidi M Sowter
    Cancer Research UK, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DU, UK
    Cancer Res 63:6130-4. 2003
    ..Remarkably, among a panel of hypoxia-inducible genes, responses were critically dependent on Hif-1 alpha but not Hif-2 alpha in both endothelial and breast cancer cells but critically dependent on Hif-2 alpha in renal carcinoma cells...
  85. ncbi Leu-574 of human HIF-1alpha is a molecular determinant of prolyl hydroxylation
    Yukio Kageyama
    Laboratory of Human Carcinogenesis, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    FASEB J 18:1028-30. 2004
    ..Hence, our findings indicate that Leu-574 is essential for recruiting PHD2/HPH2, thereby providing a molecular basis for modulating HIF-1alpha activity...
  86. ncbi Oxygen sensing by HIF hydroxylases
    Christopher J Schofield
    The Oxford Centre for Molecular Sciences and The Dyson Perrins Laboratory, Department of Chemistry, South Parks Road, Oxford OX1 3QY, UK
    Nat Rev Mol Cell Biol 5:343-54. 2004
  87. ncbi HIF hydroxylation and cellular oxygen sensing
    Eric Metzen
    Institute of Physiology, University of Lubeck, Ratzeburger Allee 160, D 23538 Lubeck, Germany
    Biol Chem 385:223-30. 2004
    ..Regulation of the amount of hydroxylase protein, and the supply of other co-substrates and co-factors, particularly the cellular availability of iron, also contribute to tuning the physiological response to hypoxia...
  88. doi Molecular mechanisms of carbonic anhydrase IX-mediated pH regulation under hypoxia
    Silvia Pastorekova
    Centre of Molecular Medicine, Institute of Virology, Slovak Academy of Sciences, Bratislava, Slovak Republic
    BJU Int 101:8-15. 2008
  89. ncbi HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: novel role of fumarate in regulation of HIF stability
    Jennifer S Isaacs
    Urologic Oncology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA
    Cancer Cell 8:143-53. 2005
    ..Further, we show that fumarate acts as a competitive inhibitor of HPH. These data delineate a novel fumarate-dependent pathway for regulating HPH activity and HIF protein levels...
  90. pmc Reversion of lethality and growth defects in Fatiga oxygen-sensor mutant flies by loss of hypoxia-inducible factor-alpha/Sima
    Lazaro Centanin
    Instituto Leloir and IIB, FCEyN Universidad de Buenos Aires, CONICET, Patricias Argentinas 435, Buenos Aires 1405, Argentina
    EMBO Rep 6:1070-5. 2005
    ..These results indicate that the main functions of Fatiga in development, including control of cell size, involve the regulation of dHIF/Sima...
  91. ncbi The use of dioxygen by HIF prolyl hydroxylase (PHD1)
    Luke A McNeill
    Oxford Centre for Molecular Sciences, Dyson Perrins Laboratory, South Parks Road, Oxford OX1 3QY, UK
    Bioorg Med Chem Lett 12:1547-50. 2002
    ..Mutation of the arginine proposed to bind 2-oxoglutarate and of the 2His-1-carboxylate iron(II) binding motif in PHD1 dramatically reduces its activity. The source of the oxygen of the product alcohol is (>95%) dioxygen...
  92. ncbi Delivery of erythropoietin by encapsulated myoblasts in a genetic model of severe anemia
    Christopher Rinsch
    Modex Thérapeutiques, Lausanne, Switzerland
    Kidney Int 62:1395-401. 2002
    ..This phenotype makes it a particularly interesting mouse model for testing erythropoietin (Epo)-based gene transfer strategies...
  93. ncbi Signalling hypoxia by HIF hydroxylases
    Christopher J Schofield
    Oxford Centre for Molecular Sciences, Department of Chemistry, Mansfield Road, Oxford OX1 3TA, UK
    Biochem Biophys Res Commun 338:617-26. 2005
    ..We review biochemical and physiological data that demonstrate a central role for these oxygenases in integrating multiple signals that coordinate cellular responses to hypoxia...
  94. pmc Disruption of dimerization and substrate phosphorylation inhibit factor inhibiting hypoxia-inducible factor (FIH) activity
    David E Lancaster
    Department of Chemistry and the Oxford Centre for Molecular Sciences, Chemistry Research Laboratory, Mansfield Road, Oxford OX1 3TA, UK
    Biochem J 383:429-37. 2004
    ..Consistent with this, we show that phosphorylation of Thr-796 prevents the hydroxylation of Asn-803 by FIH...
  95. ncbi Genotype at a promoter polymorphism of the interleukin-6 gene is associated with baseline levels of plasma C-reactive protein
    Mark A Vickers
    Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, UK
    Cardiovasc Res 53:1029-34. 2002
    ..We hypothesised that plasma CRP would be a heritable phenotype that would be influenced by genotype at this polymorphism...