Research Topics
Genomes and Genes
| Peter J RatcliffeSummaryAffiliation: University of Oxford Country: UK Publications
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Detail Information
Publications
Oxygen sensing and hypoxia signalling pathways in animals: the implications of physiology for cancerPeter J Ratcliffe
P 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...
From erythropoietin to oxygen: hypoxia-inducible factor hydroxylases and the hypoxia signal pathwayPeter J Ratcliffe
Renal and Cell Physiology Group, The Henry Wellcome Building of Genomic Medicine, University of Oxford, UK
Blood Purif 20:445-50. 2002....- 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... - 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.... - 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... - Determination and comparison of specific activity of the HIF-prolyl hydroxylasesJason R Tuckerman
Henry Wellcome Building for Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN, UK
FEBS Lett 576:145-50. 2004.... - 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.... 
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...- Differential function of the prolyl hydroxylases PHD1, PHD2, and PHD3 in the regulation of hypoxia-inducible factorRebecca J Appelhoff
Henry Wellcome Bldg of Genomic Medicine, Roosevelt Drive, Headington, Oxford, UK
J Biol Chem 279:38458-65. 2004.... - Regulation of Jumonji-domain-containing histone demethylases by hypoxia-inducible factor (HIF)-1alphaPatrick 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... - Contrasting properties of hypoxia-inducible factor 1 (HIF-1) and HIF-2 in von Hippel-Lindau-associated renal cell carcinomaRaju 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... - The HIF prolyl hydroxylase PHD3 is a potential substrate of the TRiC chaperoninNorma 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... - Interaction of hydroxylated collagen IV with the von hippel-lindau tumor suppressorAlexandra 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... - Factor-inhibiting hypoxia-inducible factor (FIH) catalyses the post-translational hydroxylation of histidinyl residues within ankyrin repeat domainsMing 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... - Regulation of growth differentiation factor 15 expression by intracellular ironSamira 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... - Asparaginyl hydroxylation of the Notch ankyrin repeat domain by factor inhibiting hypoxia-inducible factorMathew 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... - Proteomics-based identification of novel factor inhibiting hypoxia-inducible factor (FIH) substrates indicates widespread asparaginyl hydroxylation of ankyrin repeat domain-containing proteinsMatthew 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... - The FIH hydroxylase is a cellular peroxide sensor that modulates HIF transcriptional activityNorma 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... - Renal cyst formation in Fh1-deficient mice is independent of the Hif/Phd pathway: roles for fumarate in KEAP1 succination and Nrf2 signalingJulie Adam
Nuffield Department of Medicine, Henry Wellcome Building for Molecular Physiology, University of Oxford, Oxford OX3 7BN, UK
Cancer Cell 20:524-37. 2011.... - Asparagine and aspartate hydroxylation of the cytoskeletal ankyrin family is catalyzed by factor-inhibiting hypoxia-inducible factorMing 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.... - Characterization of different isoforms of the HIF prolyl hydroxylase PHD1 generated by alternative initiationYa 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... - Oxygenase-catalyzed ribosome hydroxylation occurs in prokaryotes and humansWei 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... - 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... - Genome-wide association of hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha DNA binding with expression profiling of hypoxia-inducible transcriptsDavid 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... - Cardiopulmonary function in two human disorders of the hypoxia-inducible factor (HIF) pathway: von Hippel-Lindau disease and HIF-2alpha gain-of-function mutationFederico Formenti
Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Rd, Oxford, OX1 3PT, UK
FASEB J 25:2001-11. 2011.... - Quantitative mass spectrometry reveals dynamics of factor-inhibiting hypoxia-inducible factor-catalyzed hydroxylationRachelle 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... - 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 complexDavid R Mole
Henry Wellcome Building for Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN, UK
Adv Enzyme Regul 42:333-47. 2002 - Peptide blockade of HIFalpha degradation modulates cellular metabolism and angiogenesisCarsten 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... - The prolyl hydroxylase enzymes that act as oxygen sensors regulating destruction of hypoxia-inducible factor alphaCarsten Willam
Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK
Adv Enzyme Regul 44:75-92. 2004 - Asparagine beta-hydroxylation stabilizes the ankyrin repeat domain foldLeanne 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... - Regulation of type II transmembrane serine proteinase TMPRSS6 by hypoxia-inducible factors: new link between hypoxia signaling and iron homeostasisSamira 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... - 2-oxoglutarate analogue inhibitors of HIF prolyl hydroxylaseDavid 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... - HIF prolyl hydroxylases in the rat; organ distribution and changes in expression following hypoxia and coronary artery ligationCarsten 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... - Studies on the activity of the hypoxia-inducible-factor hydroxylases using an oxygen consumption assayDominic 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.... - 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.... - HIF prolyl and asparaginyl hydroxylases in the biological response to intracellular O(2) levelsNorma 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... - Differential sensitivity of hypoxia inducible factor hydroxylation sites to hypoxia and hydroxylase inhibitorsYa 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.... - Dual-action inhibitors of HIF prolyl hydroxylases that induce binding of a second iron ionKar 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... - Hypoxia-inducible factor prolyl-hydroxylase: purification and assays of PHD2Kirsty 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... - The increase in pulmonary arterial pressure caused by hypoxia depends on iron statusThomas 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... - Mutation of von Hippel-Lindau tumour suppressor and human cardiopulmonary physiologyThomas 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... - Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1 alphaJonathan 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... - The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylasesRasheduzzaman Chowdhury
Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK
EMBO Rep 12:463-9. 2011.... - Concordant regulation of gene expression by hypoxia and 2-oxoglutarate-dependent dioxygenase inhibition: the role of HIF-1alpha, HIF-2alpha, and other pathwaysGareth 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... - Regulation of angiogenesis by hypoxia: role of the HIF systemChristopher 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... - Roles of individual prolyl-4-hydroxylase isoforms in the first 24 hours following transient focal cerebral ischaemia: insights from genetically modified miceRuo 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... - Common genetic variants at the 11q13.3 renal cancer susceptibility locus influence binding of HIF to an enhancer of cyclin D1 expressionJohannes 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... - Dynamic combinatorial chemistry employing boronic acids/boronate esters leads to potent oxygenase inhibitorsMarina 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... - Structural basis for the recognition of hydroxyproline in HIF-1 alpha by pVHLWai 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... - PHF8, a gene associated with cleft lip/palate and mental retardation, encodes for an Nepsilon-dimethyl lysine demethylaseChristoph 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... - FIH-dependent asparaginyl hydroxylation of ankyrin repeat domain-containing proteinsMatthew E Cockman
Henry Wellcome Building for Molecular Physiology, University of Oxford, Oxford, United Kingdom
Ann N Y Acad Sci 1177:9-18. 2009.... - High-resolution genome-wide mapping of HIF-binding sites by ChIP-seqJohannes Schödel
Henry Wellcome Building for Molecular Physiology, University of Oxford, Oxford, UK
Blood 117:e207-17. 2011.... - Regulation of human metabolism by hypoxia-inducible factorFederico 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... - Analysis of von Hippel-Lindau tumor suppressor as a mediator of cellular oxygen sensingNorma Masson
The Henry Wellcome Building of Genomic Medicine, University of Oxford, United Kingdom
Methods Enzymol 381:305-20. 2004 - A photoreactive small-molecule probe for 2-oxoglutarate oxygenasesDante 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... - Dysregulation of hypoxia pathways in fumarate hydratase-deficient cells is independent of defective mitochondrial metabolismLinda 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... - HIF activation identifies early lesions in VHL kidneys: evidence for site-specific tumor suppressor function in the nephronStefano 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... - 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 1Helen 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... - Genetic analysis of pathways regulated by the von Hippel-Lindau tumor suppressor in Caenorhabditis elegansTammie Bishop
The Henry Wellcome Building of Genomic Medicine, University of Oxford, Oxford, United Kingdom
PLoS Biol 2:e289. 2004.... - Aberrant succination of proteins in fumarate hydratase-deficient mice and HLRCC patients is a robust biomarker of mutation statusChiara 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... - Photoactivable peptides for identifying enzyme-substrate and protein-protein interactionsDante 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... - Cellular oxygen sensing in health and diseaseDavid R Mole
University of Oxford, Headington Campus, Roosevelt Drive, Oxford, UK
Pediatr Nephrol 23:681-94. 2008.... - Oxygen sensors and angiogenesisPatrick 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... - Oxygen sensing and hypoxia-induced responsesMathew L Coleman
Henry Wellcome Building for Molecular Physiology, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, U K
Essays Biochem 43:1-15. 2007.... - The human side of hypoxia-inducible factorThomas 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... - The hypoxia-inducible transcription factor pathway regulates oxygen sensing in the simplest animal, Trichoplax adhaerensChristoph 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... - 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 diseaseColin 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... - Abnormal sympathoadrenal development and systemic hypotension in PHD3-/- miceTammie 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... - Regulation of HIF: prolyl hydroxylasesIneke P Stolze
Henry Wellcome Building for Molecular Physiology, Roosevelt Drive, Oxford OX3 7BN, UK
Novartis Found Symp 272:15-25; discussion 25-36. 2006.... - Novel Insights into FH-associated Disease are KEAPing the Lid on Oncogenic HIF SignallingJulie 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... - Oxygen sensing by HIF hydroxylasesChristopher 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 - Control of the hypoxic response in Drosophila melanogaster by the basic helix-loop-helix PAS protein similarSofía 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... - HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: novel role of fumarate in regulation of HIF stabilityJennifer 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... - Expression of hypoxia-inducible factor-1alpha and -2alpha in hypoxic and ischemic rat kidneysChristian Rosenberger
Department of Nephrology and Medical Intensive Care, Charit, 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... - Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural familyKirsty 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.... - Expression of hypoxia-inducible factors in human renal cancer: relationship to angiogenesis and to the von Hippel-Lindau gene mutationKevin 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... - Reversion of lethality and growth defects in Fatiga oxygen-sensor mutant flies by loss of hypoxia-inducible factor-alpha/SimaLazaro 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... - Predominant role of hypoxia-inducible transcription factor (Hif)-1alpha versus Hif-2alpha in regulation of the transcriptional response to hypoxiaHeidi 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... - Widespread hypoxia-inducible expression of HIF-2alpha in distinct cell populations of different organsMichael S Wiesener
Department of Nephrology and Medical Intensive Care, Charit, 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... - New insights into an enigmatic tumour suppressorPeter J Ratcliffe
Nat Cell Biol 5:7-8. 2003 - Leu-574 of human HIF-1alpha is a molecular determinant of prolyl hydroxylationYukio 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... - HIF hydroxylation and cellular oxygen sensingEric 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... - Molecular mechanisms of carbonic anhydrase IX-mediated pH regulation under hypoxiaSilvia Pastorekova
Centre of Molecular Medicine, Institute of Virology, Slovak Academy of Sciences, Bratislava, Slovak Republic
BJU Int 101:8-15. 2008 - Effect of ascorbate on the activity of hypoxia-inducible factor in cancer cellsHelen 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... - ExCITED about HIFShoumo Bhattacharya
Nat Struct Biol 10:501-3. 2003 - Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathwayWilliam 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... - Analogues of dealanylalahopcin are inhibitors of human HIF prolyl hydroxylasesImre 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... - Signalling hypoxia by HIF hydroxylasesChristopher 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... - Disruption of dimerization and substrate phosphorylation inhibit factor inhibiting hypoxia-inducible factor (FIH) activityDavid 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... - 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... - Delivery of erythropoietin by encapsulated myoblasts in a genetic model of severe anemiaChristopher Rinsch
, Lausanne, Switzerland
Kidney Int 62:1395-401. 2002..By preventing this reaction using immunosuppression, we demonstrate that encapsulated myoblasts can deliver therapeutic doses of mouse Epo systemically and restore hemopoiesis in a genetic model of severe anemia... - Genotype at a promoter polymorphism of the interleukin-6 gene is associated with baseline levels of plasma C-reactive proteinMark 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...