HIF-1 alpha

Summary

Gene Symbol: HIF-1 alpha
Description: hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)
Alias: HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1, PASD8, bHLHe78, ARNT interacting protein, ARNT-interacting protein, HIF-1-alpha, PAS domain-containing protein 8, basic-helix-loop-helix-PAS protein MOP1, class E basic helix-loop-helix protein 78, hypoxia-inducible factor 1 alpha isoform I.3, hypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor), hypoxia-inducible factor1alpha, member of PAS protein 1, member of PAS superfamily 1
Species: human

Top Publications

  1. ncbi Hypoxia-inducible factor-1alpha is associated with angiogenesis, and expression of bFGF, PDGF-BB, and EGFR in invasive breast cancer
    R Bos
    Department of Pathology, VU University Medical Centre, Amsterdam, Netherlands
    Histopathology 46:31-6. 2005
  2. doi Hypoxia-independent activation of HIF-1 by enterobacteriaceae and their siderophores
    Hanna Hartmann
    Institut fur Medizinische Mikrobiologie und Hygiene, Universitatsklinikum Tubingen, Eberhard Karls Universitat, Tubingen, Germany
    Gastroenterology 134:756-67. 2008
  3. pmc Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1
    J A Forsythe
    Department of Physiology, University of Maryland School of Medicine, Baltimore, 21201, USA
    Mol Cell Biol 16:4604-13. 1996
  4. pmc Hypoxia-inducible factors and the response to hypoxic stress
    Amar J Majmundar
    Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Mol Cell 40:294-309. 2010
  5. ncbi Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation
    P Jaakkola
    The Henry Wellcome Building of Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
    Science 292:468-72. 2001
  6. pmc Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension
    G L Wang
    Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287 3914, USA
    Proc Natl Acad Sci U S A 92:5510-4. 1995
  7. ncbi The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
    P H Maxwell
    Wellcome Trust Centre for Human Genetics, Oxford, UK
    Nature 399:271-5. 1999
  8. 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
  9. doi Direct regulation of TWIST by HIF-1alpha promotes metastasis
    Muh Hwa Yang
    Institutes of Biochemistry and Molecular Biology, National Yang Ming University, No 155, Sec 2, Li Niong Street, Peitou, Taipei 112, Taiwan
    Nat Cell Biol 10:295-305. 2008
  10. pmc HIF-2alpha promotes hypoxic cell proliferation by enhancing c-myc transcriptional activity
    John D Gordan
    Abramson Family Cancer Research Institute, School of Medicine, University of Pennsylvania, 421 Curie Boulevard, Philadelphia, PA 19104, USA
    Cancer Cell 11:335-47. 2007

Research Grants

Detail Information

Publications328 found, 100 shown here

  1. ncbi Hypoxia-inducible factor-1alpha is associated with angiogenesis, and expression of bFGF, PDGF-BB, and EGFR in invasive breast cancer
    R Bos
    Department of Pathology, VU University Medical Centre, Amsterdam, Netherlands
    Histopathology 46:31-6. 2005
    ..This study investigated if angiogenesis or growth factors or their receptors are associated with HIF-1alpha in invasive breast cancer...
  2. doi Hypoxia-independent activation of HIF-1 by enterobacteriaceae and their siderophores
    Hanna Hartmann
    Institut fur Medizinische Mikrobiologie und Hygiene, Universitatsklinikum Tubingen, Eberhard Karls Universitat, Tubingen, Germany
    Gastroenterology 134:756-67. 2008
    ..However, molecular details of how bacteria activate HIF-1 remain unclear. Here, we pursued the role of bacterial siderophores in HIF-1 activation during infection with Enterobacteriaceae...
  3. pmc Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1
    J A Forsythe
    Department of Physiology, University of Maryland School of Medicine, Baltimore, 21201, USA
    Mol Cell Biol 16:4604-13. 1996
    ..VEGF mRNA was not induced by hypoxia in mutant cells that do not express the HIF-1beta (ARNT) subunit. These findings implicate HIF-1 in the activation of VEGF transcription in hypoxic cells...
  4. pmc Hypoxia-inducible factors and the response to hypoxic stress
    Amar J Majmundar
    Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Mol Cell 40:294-309. 2010
    ..PHDs), the HIFα subunits are intricately responsive to numerous other factors, including factor-inhibiting HIF1α (FIH1), sirtuins, and metabolites...
  5. ncbi Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation
    P Jaakkola
    The Henry Wellcome Building of Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
    Science 292:468-72. 2001
    ..An absolute requirement for dioxygen as a cosubstrate and iron as cofactor suggests that HIF-PH functions directly as a cellular oxygen sensor...
  6. pmc Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension
    G L Wang
    Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287 3914, USA
    Proc Natl Acad Sci U S A 92:5510-4. 1995
    ....
  7. ncbi The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
    P H Maxwell
    Wellcome Trust Centre for Human Genetics, Oxford, UK
    Nature 399:271-5. 1999
    ..Thus, constitutive HIF-1 activation may underlie the angiogenic phenotype of VHL-associated tumours. The pVHL/HIF-1 interaction provides a new focus for understanding cellular oxygen sensing...
  8. 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
    ....
  9. doi Direct regulation of TWIST by HIF-1alpha promotes metastasis
    Muh Hwa Yang
    Institutes of Biochemistry and Molecular Biology, National Yang Ming University, No 155, Sec 2, Li Niong Street, Peitou, Taipei 112, Taiwan
    Nat Cell Biol 10:295-305. 2008
    ..These results provide evidence of a key signalling pathway involving HIF-1alpha and TWIST that promotes metastasis in response to intratumoural hypoxia...
  10. pmc HIF-2alpha promotes hypoxic cell proliferation by enhancing c-myc transcriptional activity
    John D Gordan
    Abramson Family Cancer Research Institute, School of Medicine, University of Pennsylvania, 421 Curie Boulevard, Philadelphia, PA 19104, USA
    Cancer Cell 11:335-47. 2007
    ..Enhanced c-Myc activity likely contributes to HIF-2alpha-mediated neoplastic progression following loss of the VHL tumor suppressor and influences the behavior of hypoxic tumor cells...
  11. pmc A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation
    G L Semenza
    Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
    Mol Cell Biol 12:5447-54. 1992
    ..We have thus defined a functionally tripartite, 50-nt hypoxia-inducible enhancer which binds several nuclear factors, one of which is induced by hypoxia via de novo protein synthesis...
  12. pmc Hypoxia promotes fibrogenesis in vivo via HIF-1 stimulation of epithelial-to-mesenchymal transition
    Debra F Higgins
    Department of Medicine, Renal Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Clin Invest 117:3810-20. 2007
    ....
  13. ncbi HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing
    M Ivan
    Dana Farber Cancer Institute and Brigham and Women s Hospital, Howard Hughes Medical Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    Science 292:464-8. 2001
    ..Because proline hydroxylation requires molecular oxygen and Fe(2+), this protein modification may play a key role in mammalian oxygen sensing...
  14. ncbi Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1
    Dominador J Manalo
    Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Blood 105:659-69. 2005
    ....
  15. pmc RACK1 competes with HSP90 for binding to HIF-1alpha and is required for O(2)-independent and HSP90 inhibitor-induced degradation of HIF-1alpha
    Ye V Liu
    Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Mol Cell 25:207-17. 2007
    ..Thus, RACK1 is an essential component of an O(2)/PHD/VHL-independent mechanism for regulating HIF-1alpha stability through competition with HSP90 and recruitment of the Elongin-C/B ubiquitin ligase complex...
  16. pmc SIRT3 opposes reprogramming of cancer cell metabolism through HIF1α destabilization
    Lydia W S Finley
    Department of Pathology, The Paul F Glenn Labs for the Biological Mechanisms of Aging, Harvard Medical School, Boston, MA 02115, USA
    Cancer Cell 19:416-28. 2011
    ..Mechanistically, SIRT3 mediates metabolic reprogramming by destabilizing hypoxia-inducible factor-1α (HIF1α), a transcription factor that controls glycolytic gene expression...
  17. 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...
  18. pmc Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha
    R Ravi
    Johns Hopkins Oncology Center, Departments of Pediatrics and Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287 USA
    Genes Dev 14:34-44. 2000
    ..These results indicate that amplification of normal HIF-1-dependent responses to hypoxia via loss of p53 function contributes to the angiogenic switch during tumorigenesis...
  19. ncbi Endoglin expression is regulated by transcriptional cooperation between the hypoxia and transforming growth factor-beta pathways
    Tilman Sanchez-Elsner
    Centro de Investigaciones Biologicas, Consejo Superior de Investigaciones Cientificas, Ramiro de Maeztu 9, 28040 Madrid, Spain
    J Biol Chem 277:43799-808. 2002
    ..We propose that basal endoglin transcription (highly dependent on Sp1) may switch from a constitutive to an inducible state through Sp1 interaction with HIF-1 and Smad transcription factors, induced by hypoxia and TGF-beta, respectively...
  20. pmc Regulation of hypoxia-inducible factor-1alpha by NF-kappaB
    Patrick van Uden
    College of Life Sciences, Wellcome Trust Centre for Gene Regulation and Expression, MSI WTB JBC Complex, Dow Street, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Biochem J 412:477-84. 2008
    ..In conclusion, we find that NF-kappaB can regulate basal TNFalpha and, in certain circumstances, the hypoxia-induced HIF-1alpha...
  21. pmc Signal transduction in hypoxic cells: inducible nuclear translocation and recruitment of the CBP/p300 coactivator by the hypoxia-inducible factor-1alpha
    P J Kallio
    Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institutet, S 171 77 Stockholm, Sweden
    EMBO J 17:6573-86. 1998
    ..Thus, hypoxia-inducible nuclear import and transactivation by recruitment of CBP can be functionally separated from one another and play critical roles in signal transduction by HIF-1alpha...
  22. pmc HIF-1alpha induces cell cycle arrest by functionally counteracting Myc
    Minori Koshiji
    Laboratory of Human Carcinogenesis, NCI, National Institutes of Health, Bethesda, MD 20892, USA
    EMBO J 23:1949-56. 2004
    ..Hence, we propose that Myc is an integral part of a novel HIF-1alpha pathway, which regulates a distinct group of Myc target genes in response to hypoxia...
  23. ncbi HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells
    Ryo Fukuda
    Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Cell 129:111-22. 2007
    ..Thus, mammalian cells respond to hypoxia by altering COX subunit composition, as previously observed in yeast, but by a completely different molecular mechanism...
  24. ncbi Structure of an HIF-1alpha -pVHL complex: hydroxyproline recognition in signaling
    Jung Hyun Min
    Cellular Biochemistry and Biophysics Program and Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Science 296:1886-9. 2002
    ..Although the beta sheet-like interactions contribute to the stability of the complex, the hydroxyproline contacts are central to the strict specificity characteristic of signaling...
  25. ncbi Signal transduction to hypoxia-inducible factor 1
    Gregg Semenza
    Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, 600 North Wolfe Street, CMSC 1004, Baltimore, MD 21287 3914, USA
    Biochem Pharmacol 64:993-8. 2002
    ....
  26. ncbi p42/p44 mitogen-activated protein kinases phosphorylate hypoxia-inducible factor 1alpha (HIF-1alpha) and enhance the transcriptional activity of HIF-1
    D E Richard
    Institute of Signaling, Developmental Biology and Cancer Research, UMR CNRS 6543, Centre Antoine Lacassagne, 33 Avenue Valombrose, 06189 Nice, France
    J Biol Chem 274:32631-7. 1999
    ..This interaction between HIF-1alpha and p42/p44 MAPK suggests a cooperation between hypoxic and growth factor signals that ultimately leads to the increase in HIF-1-mediated gene expression...
  27. pmc Activation of the oxidative stress pathway by HIV-1 Vpr leads to induction of hypoxia-inducible factor 1alpha expression
    Satish L Deshmane
    Department of Neuroscience and Center for Neurovirology, Temple University School of Medicine, Philadelphia, Pennsylvania 19122, USA
    J Biol Chem 284:11364-73. 2009
    ....
  28. pmc Hypoxia-inducible factor 1 and dysregulated c-Myc cooperatively induce vascular endothelial growth factor and metabolic switches hexokinase 2 and pyruvate dehydrogenase kinase 1
    Jung whan Kim
    Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Mol Cell Biol 27:7381-93. 2007
    ....
  29. pmc Interaction with factor inhibiting HIF-1 defines an additional mode of cross-coupling between the Notch and hypoxia signaling pathways
    Xiaofeng Zheng
    Departments of Cell and Molecular Biology and Molecular Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden
    Proc Natl Acad Sci U S A 105:3368-73. 2008
    ..In conclusion, the data reveal posttranslational modification of the activated form of the Notch receptor and an intricate mode of cross-coupling between the Notch and hypoxia signaling pathways...
  30. ncbi IL-1beta-mediated up-regulation of HIF-1alpha via an NFkappaB/COX-2 pathway identifies HIF-1 as a critical link between inflammation and oncogenesis
    Yun Jin Jung
    Cell and Cancer Biology Branch, CCR, National Cancer Institute, 9610 Medical Center Dr, Suite 300, Rockville, Maryland 20850, USA
    FASEB J 17:2115-7. 2003
    ..Thus, HIF-1 is identified as a pivotal transcription factor linking the inflammatory and oncogenic pathways...
  31. ncbi Cobalt inhibits the interaction between hypoxia-inducible factor-alpha and von Hippel-Lindau protein by direct binding to hypoxia-inducible factor-alpha
    Yong Yuan
    Genome Research Institute, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267 0505, USA
    J Biol Chem 278:15911-6. 2003
    ..These findings show that cobalt mimics hypoxia, at least in part, by occupying the VHL-binding domain of HIF-alpha and thereby preventing the degradation of HIF-alpha...
  32. ncbi Stabilization of wild-type p53 by hypoxia-inducible factor 1alpha
    W G An
    Department of Cell and Cancer Biology, Medicine Branch, NCI, NIH, Bethesda, Maryland 20892, USA
    Nature 392:405-8. 1998
    ..Our results suggest that hypoxic induction of transcriptionally active wild-type p53 is achieved as a result of the stabilization of p53 by its association with HIF-1alpha...
  33. ncbi Hyperglycemia regulates hypoxia-inducible factor-1alpha protein stability and function
    Sergiu Bogdan Catrina
    Department of Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
    Diabetes 53:3226-32. 2004
    ..In conclusion, our data demonstrate that hyperglycemia impairs hypoxia-dependent protection of HIF-1alpha against proteasomal degradation and suggest a mechanism by which diabetes interferes with cellular responses to hypoxia...
  34. pmc BRCA1 tumours correlate with a HIF-1alpha phenotype and have a poor prognosis through modulation of hydroxylase enzyme profile expression
    M Yan
    Department of Pathology, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria 3002, Australia
    Br J Cancer 101:1168-74. 2009
    ..There are limited data regarding the hypoxia pathway in familial breast cancers. We therefore performed a study of hypoxic factors in BRCA1, BRCA2 and BRCAX breast cancers...
  35. pmc Regulation of HIF-1alpha and VEGF by miR-20b tunes tumor cells to adapt to the alteration of oxygen concentration
    Zhang Lei
    Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, The People s Republic of China
    PLoS ONE 4:e7629. 2009
    ..Thus, we identify a novel molecular regulation mechanism through which miR-20b regulates HIF-1alpha and VEGF and is regulated by HIF-1alpha so to keep tumor cells adapting to different oxygen concentrations...
  36. pmc Differential roles of hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha in hypoxic gene regulation
    Cheng Jun Hu
    Abramson Family Cancer Research Institute Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, PA 19104, USA
    Mol Cell Biol 23:9361-74. 2003
    ..Importantly, HIF-1alpha (and not HIF-2alpha) stimulates glycolytic gene expression in both types of cells, clearly showing for the first time that HIF-1alpha and HIF-2alpha have unique targets...
  37. pmc Downregulation of miR-199a derepresses hypoxia-inducible factor-1alpha and Sirtuin 1 and recapitulates hypoxia preconditioning in cardiac myocytes
    Shweta Rane
    Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, Division of Nephrology, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA
    Circ Res 104:879-86. 2009
    ..In addition, the data demonstrate a functional link between 2 key molecules that regulate hypoxia preconditioning and longevity...
  38. pmc HIF-1alpha binding to VHL is regulated by stimulus-sensitive proline hydroxylation
    F Yu
    Department of Pathology and Laboratory Medicine, University of Pennsylvania Cancer Center, University of Pennsylvania School of Medicine, Philadelphia 19104, USA
    Proc Natl Acad Sci U S A 98:9630-5. 2001
    ..The data furthermore show that this proline hydroxylation is the primary regulator of VHL binding...
  39. ncbi High frequency of HIF-1alpha overexpression in BRCA1 related breast cancer
    Petra van der Groep
    Department of Pathology, University Medical Center, 3508 GA, Utrecht, The Netherlands
    Breast Cancer Res Treat 111:475-80. 2008
    ..69%, P = 0.0002). Glut-1 and CAIX, downstream HIF1 targets, were expressed in 27/30 (90%) and 15/21 (71%) of hereditary cases versus 54/183 (29%) and 24/183 (13%) in ..
  40. ncbi Hypoxia-inducible factor 1 and VEGF upregulate CXCR4 in glioblastoma: implications for angiogenesis and glioma cell invasion
    David Zagzag
    Microvascular and Molecular Neuro Oncology Laboratory, New York University School of Medicine, New York, NY 10016, USA
    Lab Invest 86:1221-32. 2006
    ..We believe this knowledge may lead to a potentially important two-pronged therapy against GBM progression using chemotherapy targeting CXCR4...
  41. 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...
  42. ncbi CoCl2, a chemical inducer of hypoxia-inducible factor-1, and hypoxia reduce apoptotic cell death in hepatoma cell line HepG2
    Jean Pascal Piret
    Laboratoire de Biologie et Biochimie Cellulaire, FUNDP, 5000 Namur, Belgium
    Ann N Y Acad Sci 973:443-7. 2002
    ..These different data suggest a possible antiapoptotic role of HIF-1. More experiments are needed to define if HIF-1 actually plays an active role in cell death protection and to determine the exact mechanism underlying this effect...
  43. pmc Molecular mechanisms of transcription activation by HLF and HIF1alpha in response to hypoxia: their stabilization and redox signal-induced interaction with CBP/p300
    M Ema
    Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980 77, Japan
    EMBO J 18:1905-14. 1999
    ..Nuclear translocation of thioredoxin from cytoplasm was observed upon reducing O2 concentrations...
  44. pmc Regulation of hypoxia-inducible factor 1alpha expression and function by the mammalian target of rapamycin
    Christine C Hudson
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Mol Cell Biol 22:7004-14. 2002
    ..These studies position mTOR as an upstream activator of HIF-1 function in cancer cells and suggest that the antitumor activity of rapamycin is mediated, in part, through the inhibition of cellular responses to hypoxic stress...
  45. pmc BCL-xL is a target gene regulated by hypoxia-inducible factor-1{alpha}
    Ni Chen
    Laboratory of Pathology, Departments of Pathology and Urology, and Laboratory of Stem Cell Research, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China 610041
    J Biol Chem 284:10004-12. 2009
    ..HIF-1alpha-dependent BCL-xL overexpression may be an important mechanism by which HIF-1alpha protects prostate cancer cells from apoptosis and leads to treatment resistance...
  46. pmc Integrative analysis of HIF binding and transactivation reveals its role in maintaining histone methylation homeostasis
    Xiaobo Xia
    Department of Pediatric Oncology, Dana Farber Cancer Institute, and Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 106:4260-5. 2009
    ..These results suggest that the coordinated increase in expression of several oxygen-dependent enzymes by HIF may help compensate for decreased levels of oxygen under conditions of cellular hypoxia...
  47. pmc A potential alpha-helix motif in the amino terminus of LANA encoded by Kaposi's sarcoma-associated herpesvirus is critical for nuclear accumulation of HIF-1alpha in normoxia
    Qiliang Cai
    Department of Microbiology and the Tumor Virology Program, Abramson Comprehensive Cancer Center, University of Pennsylvania Medical School, Philadelphia, PA 19104, USA
    J Virol 81:10413-23. 2007
    ..Therefore, these data show that LANA can function not only as an inhibitor of HIF-1alpha suppressor proteins but can also induce nuclear accumulation of HIF-1alpha during KSHV latent infection...
  48. pmc Cell-type-specific regulation of degradation of hypoxia-inducible factor 1 alpha: role of subcellular compartmentalization
    Xiaowei Zheng
    Department of Cell and Molecular Biology, Karolinska Institutet, S 171 77 Stockholm, Sweden
    Mol Cell Biol 26:4628-41. 2006
    ....
  49. doi Gene expression profiling of fixed tissues identified hypoxia-inducible factor-1α, VEGF, and matrix metalloproteinase-2 as biomarkers of lymph node metastasis in hepatocellular carcinoma
    Zuo Lin Xiang
    Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
    Clin Cancer Res 17:5463-72. 2011
    ..Differential gene expression profiling is useful for investigating genes associated with lymph node metastasis (LNM). We screened genes to identify potential biomarkers for LNM in HCC...
  50. pmc 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
    ..Interestingly, PHD2 is upregulated by hypoxia, providing an HIF-1-dependent auto-regulatory mechanism driven by the oxygen tension...
  51. ncbi Signal pathway of hypoxia-inducible factor-1alpha phosphorylation and its interaction with von Hippel-Lindau tumor suppressor protein during ischemia in MiaPaCa-2 pancreatic cancer cells
    Seok J Kwon
    Department of Surgery, School of Medicine, University of Pittsburgh, PA 15213, USA
    Clin Cancer Res 11:7607-13. 2005
    ..Human pancreatic cancer MiaPaCa-2 cells were exposed to low glucose (0.1 mmol/L) with hypoxia (0.1% O(2))...
  52. doi mTORC1 signaling under hypoxic conditions is controlled by ATM-dependent phosphorylation of HIF-1α
    Hakan Cam
    Center for Childhood Cancer, Nationwide Children s Hospital, Columbus, OH 43205, USA
    Mol Cell 40:509-20. 2010
    ..Deregulation of these pathways in pediatric solid tumor xenografts suggests a link between mTORC1 dysregulation and solid tumor development and points to an important role for hypoxic regulation of mTORC1 activity in tumor development...
  53. ncbi HIF-1alpha and CA IX staining in invasive breast carcinomas: prognosis and treatment outcome
    Cynthia Trastour
    Institute of Signalling, Developmental Biology and Cancer Research, University of Nice, Nice, France
    Int J Cancer 120:1451-8. 2007
    ..CA IX is, however, a weaker prognostic and predictive factor than HIF-1alpha, and its association with HIF-1alpha does not modify the survival curve neither response to therapy, compared to HIF-1alpha alone...
  54. doi Hypoxia inducible factor 1α and hypoxia inducible factor 2α play distinct and functionally overlapping roles in oral squamous cell carcinoma
    Gui quan Zhu
    West China Hospital of Stomatology, Sichuan University, Chengdu, China
    Clin Cancer Res 16:4732-41. 2010
    ..This study aimed to investigate the functional difference between hypoxia inducible factor (HIF)-1α and HIF-2α in oral squamous cell carcinomas (OSCC)...
  55. pmc Epstein-Barr virus immortalization of human B-cells leads to stabilization of hypoxia-induced factor 1 alpha, congruent with the Warburg effect
    Suhas Darekar
    Department of Microbiology, Tumor and Cell Biology MTC, Karolinska Institutet, Stockholm, Sweden
    PLoS ONE 7:e42072. 2012
    ..The role of HIF1A in EBV-induced B-cell immortalization has not been previously studied...
  56. pmc HIF1-alpha expression predicts survival of patients with squamous cell carcinoma of the oral cavity
    Marcelo dos Santos
    Programa de Pós Graduação, Faculdade de Ciencias Medicas da Santa Casa de Sao Paulo, Sao Paulo, Sao Paulo, Brazil
    PLoS ONE 7:e45228. 2012
    ..b>HIF1α protein is associated with hypoxia response and neovascularization, essential conditions for solid tumors ..
  57. doi Hypoxia-inducible factor (HIF)-1 alpha directly enhances the transcriptional activity of stem cell factor (SCF) in response to hypoxia and epidermal growth factor (EGF)
    Zhi Bo Han
    The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, Tianjin 300020, China
    Carcinogenesis 29:1853-61. 2008
    ..Hypoxia and epidermal growth factor receptor signal coexisted in the tumor microenvironment and might promote angiogenesis through HIF-1 alpha-mediated upregulation of SCF and other angiogenic factors...
  58. doi Tumor-associated CpG demethylation augments hypoxia-induced effects by positive autoregulation of HIF-1α
    M Koslowski
    TRON Center for Translational Oncology and Immunology GmbH, Mainz, Germany
    Oncogene 30:876-82. 2011
    ..Our results provide novel and highly unexpected insights into the complexity of HIF-1α regulation in cancer cells and implicate that tumor-associated CpG demethylation augments HIF-1α-mediated effects on malignant cell growth...
  59. pmc Hypoxia inducible factor 1alpha gene (HIF-1alpha) splice variants: potential prognostic biomarkers in breast cancer
    Jean Philippe Dales
    Plateforme Transcriptome, CRO2, Marseille, France
    BMC Med 8:44. 2010
    ..The prognostic relevance of HIF-1alpha protein overexpression has been shown in breast cancer. The impact of HIF-1alpha alternative splice variant expression on breast cancer prognosis in terms of metastasis risk is not well known...
  60. pmc Involvement of hypoxia-inducible factor-1 in the inflammatory responses of human LAD2 mast cells and basophils
    Vadim V Sumbayev
    Medway School of Pharmacy, University of Kent, Chatham Maritime, United Kingdom
    PLoS ONE 7:e34259. 2012
    ..This transcription complex facilitates generation of both pro-angiogenic and inflammatory cytokines in mast cells but has a differential role in basophil stimulation comparing IgE-dependent triggering with innate immune stimuli...
  61. ncbi Hypoxia and hypoxia-inducible factor-1 alpha modulate lipopolysaccharide-induced dendritic cell activation and function
    Jonathan Jantsch
    Department of Nephrology and Hypertension, University Hospital Erlangen, Friedrich Alexander University of Erlangen Nuremberg, Erlangen, Germany
    J Immunol 180:4697-705. 2008
    ..Alltogether, our data indicate that HIF-1alpha and hypoxia play a crucial role for DC activation in inflammatory states, which is highly dependent on glycolysis even in the presence of oxygen...
  62. ncbi Hypoxia-inducible factor-1 transactivates transforming growth factor-beta3 in trophoblast
    Hirotaka Nishi
    Department of Obstetrics and Gynecology, Tokyo Medical University, 6 7 1 Nishishinjuku Shinjuku, Tokyo 160 0023, Japan
    Endocrinology 145:4113-8. 2004
    ..Our results provide evidence that regulation of TGF-beta3 promoter activity by HIF-1 represents a mechanism for trophoblast differentiation during hypoxia...
  63. doi Hypoxia inducible factor-1α in human emphysema lung tissue
    M Yasuo
    Pulmonary and Critical Care Medicine Division and Victoria Johnson Center for Obstructive Lung Diseases, Virginia Commonwealth University, Richmond, VA, USA
    Eur Respir J 37:775-83. 2011
    ..In conclusion, reduced expression of HIF-1α protein in severe COPD is consistent with the concept of a lung structure maintenance programme which is impaired on a molecular level...
  64. doi HIF-1alpha protein is an essential factor for protection of myeloid cells against LPS-induced depletion of ATP and apoptosis that supports Toll-like receptor 4-mediated production of IL-6
    Harjinder Lall
    Medway School of Pharmacy, University of Kent, United Kingdom
    Mol Immunol 45:3045-9. 2008
    ..On the other hand HIF-1alpha protein is selectively required for down-regulation of ASK1 activated during LPS-induced TLR4 downstream signalling...
  65. ncbi Vascular endothelial growth factor gene expression in colon cancer cells exposed to prostaglandin E2 is mediated by hypoxia-inducible factor 1
    Ryo Fukuda
    McKusick Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287 3914, USA
    Cancer Res 63:2330-4. 2003
    ..Thus, the activity of multiple signal transduction pathways is required for the HIF-1-mediated induction of VEGF expression in colon cancer cells exposed to PGE(2)...
  66. pmc Biochemical purification and pharmacological inhibition of a mammalian prolyl hydroxylase acting on hypoxia-inducible factor
    Mircea Ivan
    Dana Farber Cancer Institute and Brigham and Women s Hospital, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 99:13459-64. 2002
    ..A model compound of this series stabilized HIF in a variety of cells, leading to the increased production of its downstream target, vascular endothelial growth factor...
  67. ncbi Mucin 1 oncoprotein blocks hypoxia-inducible factor 1alpha activation in a survival response to hypoxia
    Li Yin
    Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 282:257-66. 2007
    ..Importantly, MUC1 also blocks hypoxia-induced apoptosis and necrosis by suppressing accumulation of ROS. These findings indicate that MUC1 attenuates HIF-1alpha activation in a survival response to hypoxic stress...
  68. pmc MCM proteins are negative regulators of hypoxia-inducible factor 1
    Maimon E Hubbi
    Graduate Training Program in Cellular and Molecular Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Mol Cell 42:700-12. 2011
    ..Exposure to hypoxia leads to MCM2-7 downregulation in diverse cell types. These studies reveal a function of MCM proteins apart from their DNA helicase activity and establish a direct link between HIF-1 and the cell-cycle machinery...
  69. ncbi Transactivation and inhibitory domains of hypoxia-inducible factor 1alpha. Modulation of transcriptional activity by oxygen tension
    B H Jiang
    Center for Medical Genetics, Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287 3914, USA
    J Biol Chem 272:19253-60. 1997
    ..These results indicate that increased transcriptional activity mediated by HIF-1 in hypoxic cells results from both increased HIF-1alpha protein levels and increased activity of HIF-1alpha transactivation domains...
  70. pmc Hypoxia-specific stabilization of HIF-1alpha by human papillomaviruses
    Mitsuhiro Nakamura
    Department of Microbiology Immunology, Northwestern University, Feinberg School of Medicine, Morton, Chicago, IL 60611, USA
    Virology 387:442-8. 2009
    ..These findings shed light on mechanisms by which HPV contributes to angiogenesis both in benign cervical lesions and in cervical cancers...
  71. ncbi Hypoxia-inducible factor 1 alpha in clear cell renal cell carcinoma
    Tobias Klatte
    Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
    Clin Cancer Res 13:7388-93. 2007
    ..Here, we evaluated the significance of HIF-1 alpha in renal cell carcinoma (RCC)...
  72. ncbi Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression
    Y Makino
    Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institutet, S 171 77 Stockholm, Sweden
    Nature 414:550-4. 2001
    ..These results indicate a previously unknown mechanism for negative regulation of angiogenesis and maintenance of an avascular phenotype...
  73. doi The HIF-1-inducible lysyl oxidase activates HIF-1 via the Akt pathway in a positive regulation loop and synergizes with HIF-1 in promoting tumor cell growth
    Floriane Pez
    CNRS Centre National de la Recherche Scientifique, FRE3310 IFR128, IBCP, Lyon, France
    Cancer Res 71:1647-57. 2011
    ..Taken together, these findings provide compelling evidence that LOX and HIF-1 act in synergy to foster tumor formation, and they suggest that HIF-1/LOX mutual regulation is a pivotal mechanism in the adaptation of tumor cells to hypoxia...
  74. pmc Adora2b-elicited Per2 stabilization promotes a HIF-dependent metabolic switch crucial for myocardial adaptation to ischemia
    Tobias Eckle
    Mucosal Inflammation Program, Department of Anesthesiology, University of Colorado Denver, Aurora, USA
    Nat Med 18:774-82. 2012
    ....
  75. pmc Epstein-Barr virus latent membrane protein 1 induces synthesis of hypoxia-inducible factor 1 alpha
    Naohiro Wakisaka
    Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599 7295, USA
    Mol Cell Biol 24:5223-34. 2004
    ..The ability of EBV, and specifically its major oncoprotein, LMP1, to induce HIF-1 alpha along with other invasiveness and angiogenic factors reported previously discloses additional oncogenic properties of this tumor virus...
  76. 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...
  77. doi MUC1, a new hypoxia inducible factor target gene, is an actor in clear renal cell carcinoma tumor progression
    Sebastien Aubert
    Institut National de Santé et de Recherche Médicale, U837, Jean Pierre Aubert Research Center, Lille, France
    Cancer Res 69:5707-15. 2009
    ..Altogether, these results show that MUC1 is directly regulated by HIF-1alpha and affects the invasive and migration properties of renal cancer cells. Thus, MUC1 could serve as a potential therapeutic target in cRCC...
  78. doi The Akt/mTOR pathway assures the synthesis of HIF-1alpha protein in a glucose- and reoxygenation-dependent manner in irradiated tumors
    Hiroshi Harada
    Department of Radiation Oncology and Image Applied Therapy, Kyoto University Graduate School of Medicine, Kyoto, Japan
    J Biol Chem 284:5332-42. 2009
    ....
  79. pmc BH3-only protein Noxa is a mediator of hypoxic cell death induced by hypoxia-inducible factor 1alpha
    Jee Youn Kim
    Department of Pathology, College of Medicine, Kyung Hee University, 1 Hoegi dong, Dongdaemoon Koo, Seoul 130 701, Korea
    J Exp Med 199:113-24. 2004
    ..Further, we show that reactive oxygen species and resultant cytochrome c release participate in Noxa-mediated hypoxic cell death. Altogether, our results show that Noxa is induced by HIF-1alpha and mediates hypoxic cell death...
  80. ncbi Recruitment of HIF-1alpha and HIF-2alpha to common target genes is differentially regulated in neuroblastoma: HIF-2alpha promotes an aggressive phenotype
    Linda Holmquist-Mengelbier
    Division of Molecular Medicine, Department of Laboratory Medicine, Lund University, University Hospital MAS, SE 205 02 Malmo, Sweden
    Cancer Cell 10:413-23. 2006
    ..Our results demonstrate the relevance of HIF-2alpha in neuroblastoma progression and have general tumor biological implications...
  81. ncbi Interaction between beta-catenin and HIF-1 promotes cellular adaptation to hypoxia
    Abderrahmane Kaidi
    Cancer Research UK Colorectal Tumour Biology Research Group, Department of Cellular and Molecular Medicine, University of Bristol, Bristol, BS8 1TD, UK
    Nat Cell Biol 9:210-7. 2007
    ..This study highlights the importance of the microenvironment in transcriptional regulation...
  82. ncbi Histone deacetylase 7 associates with hypoxia-inducible factor 1alpha and increases transcriptional activity
    Hiroyuki Kato
    Department of Molecular Cell Physiology, Tokyo Metropolitan Institute of Medical Science, 3 18 22 Honkomagome, Bunkyo ku, Tokyo 113 8613, Japan
    J Biol Chem 279:41966-74. 2004
    ..Taken together, these results indicate that HDAC7 is a novel transcriptional activator of HIF-1alpha..
  83. doi miR-20b modulates VEGF expression by targeting HIF-1 alpha and STAT3 in MCF-7 breast cancer cells
    Sandra Cascio
    Section of Medical Oncology, Department of Surgical and Oncological Sciences, Palermo University, Palermo, Italy
    J Cell Physiol 224:242-9. 2010
    ..In summary, this report demonstrates, for the first time, that the VEGF expression in breast cancer cells is mediated by HIF-1 and STAT3 in a miR-20b-dependent manner...
  84. 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...
  85. pmc 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
    ..However, here we show that chronic hypoxia induces HIF1/2alpha"desensitization" in cellulo and in mice...
  86. pmc Glioma-derived mutations in IDH1 dominantly inhibit IDH1 catalytic activity and induce HIF-1alpha
    Shimin Zhao
    Molecular and Cell Biology Laboratory, Institute of Biomedical Sciences, Fudan University, 130 Dong an Road, Shanghai 200032, China
    Science 324:261-5. 2009
    ..Thus, IDH1 appears to function as a tumor suppressor that, when mutationally inactivated, contributes to tumorigenesis in part through induction of the HIF-1 pathway...
  87. ncbi Synergistic cooperation between hypoxia and transforming growth factor-beta pathways on human vascular endothelial growth factor gene expression
    T Sanchez-Elsner
    Centro de Investigaciones Biologicas, CSIC, Velazquez 144, 28006 Madrid, Spain
    J Biol Chem 276:38527-35. 2001
    ..These results demonstrate that both TGF-beta and hypoxia signaling pathways can synergize in the regulation of VEGF gene expression at the transcriptional level...
  88. pmc FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity
    P C Mahon
    Institute of Genetic Medicine, Departments of Pediatrics and Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287 3914, USA
    Genes Dev 15:2675-86. 2001
    ..Involvement of VHL in association with FIH-1 provides a unifying mechanism for the modulation of HIF-1alpha protein stabilization and transcriptional activation in response to changes in cellular O(2) concentration...
  89. ncbi Structural and mechanistic studies on the inhibition of the hypoxia-inducible transcription factor hydroxylases by tricarboxylic acid cycle intermediates
    Kirsty S Hewitson
    Department of Chemistry, University of Oxford, Mansfield Road, Oxford OX1 3TA, United Kingdom
    J Biol Chem 282:3293-301. 2007
    ....
  90. doi Reactive oxygen species stabilize hypoxia-inducible factor-1 alpha protein and stimulate transcriptional activity via AMP-activated protein kinase in DU145 human prostate cancer cells
    Seung Nam Jung
    Department of Biochemistry and Molecular Biology, Kyung Hee University School of Medicine, Seoul 130 701, Korea
    Carcinogenesis 29:713-21. 2008
    ..Collectively, our findings identify AMPK as a key determinant of HIF-1 functions in response to ROS and its possible role in the sophisticated HIF-1 regulatory mechanisms...
  91. pmc MicroRNA-155 promotes resolution of hypoxia-inducible factor 1alpha activity during prolonged hypoxia
    Ulrike Bruning
    School of Medicine and Medical Science and UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland
    Mol Cell Biol 31:4087-96. 2011
    ....
  92. ncbi In vivo expression of mRNAs encoding hypoxia-inducible factor 1
    C M Wiener
    Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
    Biochem Biophys Res Commun 225:485-8. 1996
    ..The ubiquitous in vivo expression of HIF-1 alpha and HIF-1 beta (ARNT) mRNA is consistent with the proposed role of HIF-1 in coordinating adaptive transcriptional responses to hypoxia...
  93. ncbi Accumulation of Krebs cycle intermediates and over-expression of HIF1alpha in tumours which result from germline FH and SDH mutations
    P J Pollard
    Molecular and Population Genetics Laboratory, London WC2A 3PX, UK
    Hum Mol Genet 14:2231-9. 2005
    ..The basic mechanism of tumorigenesis in HPGL and HLRCC is likely to be pseudo-hypoxic drive, just as it is in von Hippel-Lindau syndrome...
  94. pmc High expression of HIF1a is a predictor of clinical outcome in patients with pancreatic ductal adenocarcinomas and correlated to PDGFA, VEGF, and bFGF
    Andreas Claudius Hoffmann
    Department of Biochemistry and Molecular Biology and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA
    Neoplasia 10:674-9. 2008
    ..In this study, we investigated the prognostic values of HIF1a, bFGF, VEGF, and PDGFA gene expressions as well as their interrelationships...
  95. ncbi Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch
    David Lando
    Department of Molecular Biosciences Biochemistry, Adelaide University, SA 5005, Australia
    Science 295:858-61. 2002
    ..Full induction of HIF-1alpha and -2alpha, therefore, relies on the abrogation of both Pro and Asn hydroxylation, which during normoxia occur at the degradation and COOH-terminal transactivation domains, respectively...
  96. pmc General involvement of hypoxia-inducible factor 1 in transcriptional response to hypoxia
    G L Wang
    Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205
    Proc Natl Acad Sci U S A 90:4304-8. 1993
    ..These results provide evidence that HIF-1 and its recognition sequence are common components of a general mammalian cellular response to hypoxia...
  97. ncbi MAPK signaling up-regulates the activity of hypoxia-inducible factors by its effects on p300
    Nianli Sang
    Cardeza Foundation for Hematological Research, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    J Biol Chem 278:14013-9. 2003
    ..Taken together, our data suggest that MAPK signaling facilitates HIF activation through p300/CBP...
  98. pmc Histone deacetylase inhibitors repress the transactivation potential of hypoxia-inducible factors independently of direct acetylation of HIF-alpha
    Donna M Fath
    Cardeza Foundation for Hematologic Research and Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    J Biol Chem 281:13612-9. 2006
    ....
  99. 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...
  100. ncbi Direct interactions between HIF-1 alpha and Mdm2 modulate p53 function
    Delin Chen
    Institute for Cancer Genetics, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
    J Biol Chem 278:13595-8. 2003
    ..These results have significant implications regarding the molecular mechanism by which p53 is activated by HIF-1 alpha in response to hypoxia...
  101. pmc Hypoxia up-regulates hypoxia-inducible factor-1alpha transcription by involving phosphatidylinositol 3-kinase and nuclear factor kappaB in pulmonary artery smooth muscle cells
    Rachida S BelAiba
    Experimental Pediatric Cardiology, Department of Pediatric Cardiology and Congenital Heart Disease, German Heart Center Munich at the Technical University Munich, D 80636 Munich, Germany
    Mol Biol Cell 18:4691-7. 2007
    ..Together, these findings provide a novel mechanism in which hypoxia induces HIF-1alpha mRNA expression via the PI3K/AKT pathway and activation of NFkappaB...

Research Grants67

  1. Dissecting the metastasis suppressor complex to identify colon cancer biomarkers
    Sam Thiagalingam; Fiscal Year: 2013
    ..inhibited VEGF reporter activity and Smad4 physically interacts with specific transcription factors (TFs) such as HIF1? to potentially regulat metastatic progression of colon cancer...
  2. VEGF Function in B-CLL
    Neil E Kay; Fiscal Year: 2010
    ..3) Does the VEGF/VEGF-R pathway(s) found in CLL B cells correlate with either clinical and/or critical biologic parameters in B-CLL? ..
  3. ANDV Induced Responses of Hypoxic Endothelial Cells
    Erich R Mackow; Fiscal Year: 2012
    ..growth factor (VEGF), and this response is transcriptionally directed by the hypoxia inducible factor 1? (HIF1?). ECs secrete VEGF and VEGF in turn activates VEGFR2 receptors on ECs in an autocrine and paracrine manner...
  4. Functional Significance of the HIF1 Transcriptome in Granulosa Cells
    John H Nilson; Fiscal Year: 2013
    ..HIF1a, together with constitutively expressed HIF1b, form the heterodimeric transcriptional factor HIF1 that activates a hierarchy of target genes that permit cells to survive under reduced oxygen concentrations...
  5. HEAT AND RADIATION EFFECTS ON TUMOR MICROCIRCULATION
    Mark Wesley Dewhirst; Fiscal Year: 2013
    ..We refer to this as the HRHV axis. Unregulated tumor angiogenesis is known to be tied to hypoxia, HIF1 and VEGF by our work and that of many others, however, it is unclear how the angiogenic stimulus is maintained over ..
  6. OXYGEN SENSING AND OSTEOGENESIS
    Thomas L Clemens; Fiscal Year: 2013
    ..Using a genetic approach, we have demonstrated that overexpression of HIF1 in mouse osteoblasts through disruption of Vhl profoundly increases angiogenesis and osteogenesis;these processes ..
  7. Metabolic regulation of diabetic nephropathy
    Karen Block; Fiscal Year: 2013
    ..This work may have major therapeutic implications. ..
  8. Pluripotent human stem cells as models for normal and diseased trophoblast
    ROBERT MICHAEL ROBERTS; Fiscal Year: 2013
    ..Aim 3 will examine a possible model for PE in which up-regulation of stable HIF1 alpha (HIF1A) protein is hypothesized to counteract the effects of high O2 during in vitro development of BMP-hESC and ..
  9. Regulation of Transcriptional Activity of Hypoxia Inducible Factor 2
    Cheng Jun Hu; Fiscal Year: 2012
    ..b>HIF1( and HIF2( are the two major transcription factors responding to low oxygen (hypoxia) in solid tumors...
  10. Tissue Oxygenation and Wound Healing
    Chandan K Sen; Fiscal Year: 2013
    ..b>HIF1[unreadable] is abundant in basal keratinocytes at the wound edge and causes growth arrest...
  11. The histone deacetylase SIRT6 functions as a co-repressor of Hif1 alpha in glucos
    Raul Mostoslavsky; Fiscal Year: 2013
    ....
  12. Klotho: Therapeutic Agent for Ischemia Reperfusion Induced Acute Kidney Injury
    Ming Chang Hu; Fiscal Year: 2013
    ..b>HIF1/2 activation protects the kidney from IRI...
  13. The attenuation of ischemic injury by transglutaminase 2
    Gail V W Johnson; Fiscal Year: 2013
    ..HIF, which is composed of the oxygen sensitive HIF1 subunit and the constitutively expressed HIF12, is the transcription factor that is primarily responsible for the ..
  14. Regulation of Renal Oxygenation and Blood Pressure
    Pin Lan Li; Fiscal Year: 2006
    ..abstract_text> ..
  15. Air/liquid interface cultures for alveolar type II cell differentiation
    ROBERT JAMES MASON; Fiscal Year: 2012
    ..This study should also indicate that sustained pulmonary edema will impair type I cell function and provide another reason for the use of supplemental oxygen in acute lung injury. ..
  16. HIF-1alpha, a Survival and Differentiation Factor for Cartilage
    Ernestina Schipani; Fiscal Year: 2013
    ..abstract_text> ..
  17. The von Hippel-Lindau Tumor Suppressor Protein:Roles in Cancer and Oxygen Sensing
    William G Kaelin; Fiscal Year: 2013
    ..The interaction of pVHL with HIF1 requires that HIF? be prolyl hydroxylated by members of the EglN family, which belong to a recently recognized ..
  18. Ovarian Cancer Initiating Cells: Metabolic Characterization
    Susan Kay Murphy; Fiscal Year: 2012
    ..078). HIF1[unreadable] functions as part of a key transcription factor complex regulating metabolic pathways and processes in ..
  19. Chromatin organization and transcription factor targeting in cancer
    Ian J Davis; Fiscal Year: 2013
    ..in oxygen content in tissues, leads to the stabilization of the transcription factors Hypoxia-inducible factor 1 (HIF1) and Hypoxia-inducible factor 2 (HIF2) which normally result in the transcriptional activation of a genetic program ..
  20. Transcriptional and physiological analysis of cardiac HIF1
    Ralph Shohet; Fiscal Year: 2009
    ..It is a transcription factor that is regulated by the effect of ambient oxygen concentration on its stability. HIF1 regulates a panoply of genes involved in response to hypoxia, including factors that augment angiogenesis and favor ..
  21. VEGF Regulation of Hepatic Erythropoietin Synthesis
    Calvin Kuo; Fiscal Year: 2009
    ....
  22. Plk3 in lung cancer
    Dazhong Xu; Fiscal Year: 2012
    ..The result of this study should provide significant new insights into the biology of lung cancer, the mechanism of how environmental relevant nickel metal affects lung cancer, and the potential of Plk3 as therapeutic target. ..
  23. Patient Oriented Research Program in Neuro-oncology
    Vinay K Puduvalli; Fiscal Year: 2013
    ..preclinical studies by inhibiting the escape routes including non-VEGF molecular pathways such as overexpression of HIF1[unreadable], PDGF and IGF as well as recruitment of circulating endothelial cells...
  24. ANESTHETIC-INDUCED CARDIAC PRECONDITIONING
    Zeljko J Bosnjak; Fiscal Year: 2012
    ..Our findings are likely to have a significant impact in the clinical use of volatile anesthetics. ..
  25. Dual Targeting of DNA Repair and p53 pathways for treatment of brain cancer
    KAREN ELIZABETH POLLOK; Fiscal Year: 2013
    ..The treatment strategies investigated here will use clinically relevant in vivo models and novel multi-targeting approaches and have the potential to improve treatment efficacy and quality of life for patients with GBM. ..
  26. Molecular Mechanisms of Impaired Angiogenesis in Aging Gastric Mucosa
    Andrzej S Tarnawski; Fiscal Year: 2013
    ..include analysis of: expression of proteins involved in angiogenesis - VEGF, VEGFR2, P-VEGFR2 as well as HSP90, HIF1, HIF1, importin , AMPK, P-CREB and P-STAT3;their interactions and binding of HIF1, P-CREB and P- STAT3 to the VEGF ..
  27. TGFbeta IN THE BONE MICROENVIRONMENT: ROLE IN TUMOR METASTASIS
    Theresa A Guise; Fiscal Year: 2012
    ..Aim 3 will test whether hypoxia via hypoxia-indicible factor-1( (Hif1() increases TGF( signaling in tumor cells both at the molecular level in vitro and in bone metastases in vivo...
  28. Inhibition of VEGF Signaling Pathway and Metastasis
    Yi Lu; Fiscal Year: 2010
    ....
  29. Vascular targeted pan PI-3 kinase inhibitor prodrug, SF1126 for glioma therapy
    DONALD DURDEN; Fiscal Year: 2012
    ..This proposal will provide useful information for the application of SF1126 to the treatment of malignant glial tumors in man and therefore may potentially improve survival of patients with this form of cancer. ..
  30. Anti-Tumorigenic Potential of Novel Digitoxin Analogues
    Anand K Iyer; Fiscal Year: 2013
    ..data showing potent anti- angiogenic potential for MonoD, and inhibition of the key angiogenic mediators Akt and HIF1[unreadable]...
  31. The Role of HIF-1 in Neurogenic and Behavior Responses to Antidepressants.
    W TIMOTHY O'BRIEN; Fiscal Year: 2013
    ..A new connection between hypoxia signaling and the actions antidepressants could lead to a better understanding of and new approaches to the treatment of affective disorders. ..
  32. HIF-1 Regulation of macrophages in Injured Spinal Cord
    DUSTIN JAMES DONNELLY; Fiscal Year: 2010
    ..Studies in this proposal will examine how the lesion microenvironment drives macrophage inflammatory function. HIF1 is a ubiquitous transcription factor regulating the cellular response to hypoxia...
  33. The role of HIF2alpha in colon carcinogenesis
    Yatrik M Shah; Fiscal Year: 2013
    ..Ultimately these studies will determine if HIF2a is a potential therapeutic target in colon inflammation and may provide an alternative strategy for preventing and treating colon cancer. ..
  34. HIF Regulation of Enteric Beta Defensins
    Caleb James Kelly; Fiscal Year: 2013
    ..Finally, a plan is in place to develop the research and academic skills of the applicant to provide training in all aspects necessary for a productive career as a physician scientist. ..
  35. Role of Protein Acetylation in Diabetic kidney Disease
    John C He; Fiscal Year: 2013
    ..In addition to FOXO4, the acetylation of NFkB, STAT3, p53, HIF1[unreadable], and Smad3 also modulates their target gene expression and these transcription factors (TFs) are known ..
  36. The Role of miR-122 in Alcoholic Liver Disease
    Abhishek Satishchandran; Fiscal Year: 2013
    ..Bioinformatic miRNA target prediction tools suggest Hypoxia-Inducible Factor 1-[unreadable] (HIF1[unreadable]) is a primary target of miR-122. HIF1[unreadable] is critical to the progression of ALD...
  37. Control of iron absorption by intestinal HIF2 in iron and hematological disorders
    Yatrik M Shah; Fiscal Year: 2013
    ..Hypoxia-inducible factors (HIFs) are heterodimeric transcription factors consisting of an alpha-subunit (HIF1-alpha or HIF2-alpha) and beta-subunit (aryl hydrocarbon nuclear translocator (ARNT)...
  38. Regenerative wound healing via inflammation-modulating biomaterials
    Phillip B Messersmith; Fiscal Year: 2013
    ....
  39. Control of Toxoplasma gondii Growth by the Host Cell Transcription Factor HIF1
    Ira J Blader; Fiscal Year: 2013
    ..These studies are likely to provide important information regarding the interaction between Toxoplasma and its host cell. ..
  40. The Regulatory Role of PTEN on CXCR4-mediated Metastasis in Prostate Cancer Cells
    MAHANDRANAUTH ANAND CHETRAM; Fiscal Year: 2011
    ..Furthermore we will determine whether ROS up-regulation of CXCR4 is through the PI3K/AKT/HIF1[unreadable] pathway by western blot analysis and luciferase assay;(iii) determine whether ROS promotes CXCR4-..
  41. ADSS1 inactivation as a promoter of tumor metabolism and lung carcinogenesis
    Christopher R Herzog; Fiscal Year: 2010
    ..The functional relationship between ADSS1, LKB1, AMPK and HIF1 will be the focus of this investigation...
  42. Dietary Supplement Selenium and HIF-1alpha Regulation in Cancer
    Sreenivasulu Chintala; Fiscal Year: 2010
    ..Successful completion of the studies proposed will establish the role of Se in inhibiting HIF-11 in cancer and other disease for a disease free maintenance of life across the life span of an individual. ..
  43. Melanocyte Survival and Transformation: Hypoxia & P13 Kinase/Akt/mTOR Signaling
    Marianne Broome Powell; Fiscal Year: 2010
    ....
  44. The Role of HIF-1alpha in Breast Cancer Stem Cell Activity
    TIFFANY NICOLE SEAGROVES; Fiscal Year: 2013
    ....
  45. Imaging and Modifying Hypoxia in Head and Neck Squamous Cell Tumors
    Sydney M Evans; Fiscal Year: 2013
    ..Tissue collected at surgery will be used to assay hypoxia-related biological endpoints including HIF1?, proliferation (Ki67), blood vessels (CD31), apoptosis and pAkt (radiation resistance) and osteopontin (OPN) in ..
  46. ROS and HIFa as molecular targets for chemoprevention in Sirt3 -/- breast cancers
    David Gius; Fiscal Year: 2013
    ..We hypothesize that agents thought to scavenge or decrease cellular ROS (O2-.) and/or inhibit HIF-1[unreadable] activity will prevent tumors in Sirt3 knockout mice. ..
  47. Microelectrode oxygenation control of tumor necrosis
    Neil Forbes; Fiscal Year: 2006
    ..cell death, and determine the extent that poor oxygenation causes tumor necrosis; and 3) demonstrate that a HIF1-alpha response is critical for cell survival in hypoxic tumor tissue...
  48. Oxygen Therapy in Neonatal Hypoxia-Ischemia
    John Zhang; Fiscal Year: 2007
    ..Our specific hypothesis is that the level and expression of inflammatory cytokines and iNOS increased in injured brain tissues and lead to cell death. ..
  49. PlGF-HIF1a-miRNA Axis in Sickle Pulmonary Hypertension
    Punam Malik; Fiscal Year: 2013
    ..These studies will likely provide new diagnostic bio-markers for assessment of PHT, and novel therapeutic targets for a disease that currently has few or no therapeutic options. ..
  50. Alcoholic Liver Dysfunction Potentiation by Hyperlipidemia and Cigarette Smoke
    SHANNON MARIE BAILEY; Fiscal Year: 2013
    ....
  51. HPV, Tumor Metabolism and Radiosensitivity in Head and Neck Cancer
    Hyeong Reh Choi Kim; Fiscal Year: 2013
    ..mutant into oral keratinocytes, mimicking smoking-associated cancer, results in upregulation of hypoxia signaling (HIF1) pathway, which in turn could increase glucose metabolism, whereas introduction of HPV16-E6 into those cells leads ..
  52. HIF-1alpha Mediated Wound Healing in Periapical Lesion
    Hajime Sasaki; Fiscal Year: 2013
    ..These outcomes are targeted to novel treatment strategies to improve the healing process in dentoalveolar infections that will have potential application in other chronic fibrotic and granulomatous diseases. ..
  53. Renal medullary HIF prolyl hydroxylases and salt sensitivity of blood pressure
    Ningjun Li; Fiscal Year: 2013
    ..The proposed studies will reveal a novel molecular mechanism mediating renal adaptation to high salt intake and provide new insights into the pathogenesis of salt-sensitive hypertension. ..
  54. Control by Oxygen of Lens Metabolism and Cataract Formation
    David Beebe; Fiscal Year: 2009
    ..This study will test our prediction that oxygen from the retina is responsible for the "normal," age- related opacification of the lens nucleus. ..
  55. CCN proteins in cartilage formation and maintenance
    Karen M Lyons; Fiscal Year: 2013
    ..This knowledge has the potential to lead to new therapeutic approaches to the treatment of OA and DDD. ..
  56. A Critical Role for the Microvasculature in Airway Transplantation
    MARK ROBERT NICOLLS; Fiscal Year: 2013
    ..The proposed studies will investigate how the body's normal reparative processes resupply airways with blood vessels and how this process might be utilized to prevent airway injury. ..
  57. Metabolic Control of Endothelias Cell Phenotype
    Kenneth Walsh; Fiscal Year: 2013
    ..With these proposed studies, we hope develop a better understanding of how endothelium functions at the interface of cardiovascular disease and metabolic dysfunction. ..
  58. Chaetocin as a Potential Therapy for Multiple Myeloma
    Keith C Bible; Fiscal Year: 2012
    ..the contributions of effects on TrxR and other reductases, histone modifying enzymes (including HDACs and HMTs), HIF1 and other targets to the cytotoxic selectivity of chaetocin;as well as further investigate mechanisms of cellular ..
  59. Molecular Basis Of Renal Cell Carcinoma Response to SU11428
    Robert J Motzer; Fiscal Year: 2011
    ..These tumor and cell line-based studies lay a foundation for further molecular studies aimed at understanding the sensitivity/resistance of RCC to SU11248. ..
  60. Mechanisms of tumor suppression by the chromatin deacetylase SIRT6
    DAVID BENNER LOMBARD; Fiscal Year: 2013
    ..SIRT6 functions as an intestinal tumor suppressor in humans and mice, at least in part via attenuation of MYC and HIF1 signaling...
  61. Targeting MUC1-induced Tumor-stromal Metabolic Cross-talk in Pancreatic Cancer
    Pankaj Kumar Singh; Fiscal Year: 2013
    ..Here, we hypothesize that signaling through MUC1 stabilizes HIF1??and facilitates metabolic cross-talk between epithelial and stromal components in pancreatic adenocarcinoma;thus ..
  62. Role of HIF-1a in T Cells During Sepsis
    Charles Caldwell; Fiscal Year: 2009
    ..These studies will greatly advance our knowledge of the pathophysiology of sepsis and may identify several novel potential therapeutic targets. ..
  63. Targeted Elimination of Cancer Stem Cells for AML Therapy
    SAMI NIMER MALEK; Fiscal Year: 2013
    ..Through these efforts, we have established an essential role for hypoxia-inducing factor 1 [unreadable] (HIF1 [unreadable]) in the maintenance of the stem cells of both lymphoma and leukemia...
  64. Hypoxia-inducible factors in alcoholic liver disease
    Gyongyi Szabo; Fiscal Year: 2010
    ..protein and mRNA in the livers of chronically alcohol-fed mice versus pair-fed controls correlate positively with HIF1 or HIF2 transcription factor activity and expression of downstream targets of HIF1 and HIF2 that are implicated in ..
  65. Regulation of Hypoxia Inducible Factor-1 by Nitric Oxide
    Lisa Palmer; Fiscal Year: 2004
    ..At the completion of this project, we believe we will have identified several new targets for the prevention and treatment of hypoxia- induced and primary pulmonary hypertension. ..
  66. A Pilot Study of Novel Candidate Genes for Preeclampsia
    Sue Ingles; Fiscal Year: 2005
    ..While the likely severity of such bias has been debated in the epidemiologic literature, there have been no studies to assess the extent of this problem in Hispanics, one of the populations that is most likely to be affected. ..
  67. Hypoxia Signaling, Chromatin Remodeling and Nickel Carcinogenesis
    Max Costa; Fiscal Year: 2009
    ..These studies will allow us to understand the importance of hypoxia signaling and the HIF-1alpha transcription factor in promoting neoplastic cell transformation. ..