Skip to main content
SpringerLink
Log in

Hypoxia-Inducible Factor-1 Signaling System

  • Chapter
  • First Online:
Signaling Pathways in Liver Diseases

  • 1544 Accesses

Abstract

Oxygen (O2) homeostasis is regulated by balancing the supply of O2 from the vasculature and O2 consumed by mitochondrial oxidative phosphorylation. If the balance of O2 is disturbed, cells are exposed to a state of either oxidative stress or oxidative depression. Hypoxia is a state of oxidative depression and occurs when there is a reduction in blood flow or O2 content of the blood. In the liver, as within other tissues, hypoxic cells initiate adaptive responses to help ensure their survival. These adaptive responses are aimed at increasing O2 supply and compensate for loss of energy via physiological, metabolic, and molecular mechanisms. Studies are continuing to define the molecular pathways of these mechanisms and reveal that they occur at every regulatory level, including gene transcription, protein translation, and posttranslational modifications.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Miyake T, Kung CK, Goldwasser E (1977) Purification of human erythropoietin. J Biol Chem 252:5558–5564

    PubMed  CAS  Google Scholar 

  2. Koury ST, Bondurant MC, Koury MJ, Semenza GL (1991) Localization of cells producing erythropoietin in murine liver by in situ hybridization. Blood 77:2497–2503

    PubMed  CAS  Google Scholar 

  3. Semenza GL, Nejfelt MK, Chi SM, Antonarakis SE (1991) Hypoxia-inducible nuclear factors bind to an enhancer element located 3' to the human erythropoietin gene. Proc Natl Acad Sci U S A 88:5680–5684

    PubMed  CAS  Google Scholar 

  4. Beck I, Ramirez S, Weinmann R, Caro J (1991) Enhancer element at the 3'-flanking region controls transcriptional response to hypoxia in the human erythropoietin gene. J Biol Chem 266:15563–15566

    PubMed  CAS  Google Scholar 

  5. Pugh CW, Tan CC, Jones RW, Ratcliffe PJ (1991) Functional analysis of an oxygen-regulated transcriptional enhancer lying 3' to the mouse erythropoietin gene. Proc Natl Acad Sci U S A 88:10553–10557

    PubMed  CAS  Google Scholar 

  6. Wang GL, Semenza GL (1993) Characterization of hypoxia-inducible factor 1 and regulation of DNA binding activity by hypoxia. J Biol Chem 268:21513–21518

    PubMed  CAS  Google Scholar 

  7. Beck I, Weinmann R, Caro J (1993) Characterization of hypoxia-responsive enhancer in the human erythropoietin gene shows presence of hypoxia-inducible 120-Kd nuclear DNA-binding protein in erythropoietin-producing and nonproducing cells. Blood 82:704–711

    PubMed  CAS  Google Scholar 

  8. Maxwell PH, Pugh CW, Ratcliffe PJ (1993) Inducible operation of the erythropoietin 3' enhancer in multiple cell lines: evidence for a widespread oxygen-sensing mechanism. Proc Natl Acad Sci U S A 90:2423–2427

    PubMed  CAS  Google Scholar 

  9. Wang GL, Semenza GL (1993) General involvement of hypoxia-inducible factor 1 in transcriptional response to hypoxia. Proc Natl Acad Sci U S A 90:4304–4308

    PubMed  CAS  Google Scholar 

  10. Semenza GL, Wang GL (1992) 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. Mol Cell Biol 12:5447–5454

    PubMed  CAS  Google Scholar 

  11. Wang GL, Jiang BH, Rue EA, Semenza GL (1995) Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci U S A 92:5510–5514

    PubMed  CAS  Google Scholar 

  12. Wang GL, Semenza GL (1995) Purification and characterization of hypoxia-inducible factor 1. J Biol Chem 270: 1230–1237

    PubMed  CAS  Google Scholar 

  13. Huang ZJ, Edery I, Rosbash M (1993) PAS is a dimerization domain common to Drosophila period and several transcription factors. Nature 364:259–262

    PubMed  CAS  Google Scholar 

  14. Pugh CW, O’Rourke JF, Nagao M, Gleadle JM, Ratcliffe PJ (1997) Activation of hypoxia-inducible factor-1; definition of regulatory domains within the alpha subunit. J Biol Chem 272:11205–11214

    PubMed  CAS  Google Scholar 

  15. Hogenesch JB, Chan WK, Jackiw VH, Brown RC, Gu YZ, Pray-Grant M, Perdew GH, Bradfield CA (1997) Charac­terization of a subset of the basic-helix-loop-helix-PAS superfamily that interacts with components of the dioxin signaling pathway. J Biol Chem 272:8581–8593

    PubMed  CAS  Google Scholar 

  16. Kietzmann T, Cornesse Y, Brechtel K, Modaressi S, Junger­mann K (2001) Perivenous expression of the mRNA of the three hypoxia-inducible factor alpha-subunits, HIF1alpha, HIF2alpha and HIF3alpha, in rat liver. Biochem J 354: 531–537

    PubMed  CAS  Google Scholar 

  17. Gu YZ, Moran SM, Hogenesch JB, Wartman L, Bradfield CA (1998) Molecular characterization and chromosomal localization of a third alpha-class hypoxia inducible factor subunit, HIF3alpha. Gene Expr 7:205–213

    PubMed  CAS  Google Scholar 

  18. Tian H, McKnight SL, Russell DW (1997) Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells. Genes Dev 11:72–82

    PubMed  CAS  Google Scholar 

  19. Ema M, Taya S, Yokotani N, Sogawa K, Matsuda Y, Fujii-Kuriyama Y (1997) A novel bHLH-PAS factor with close sequence similarity to hypoxia-inducible factor 1alpha regulates the VEGF expression and is potentially involved in lung and vascular development. Proc Natl Acad Sci U S A 94:4273–4278

    PubMed  CAS  Google Scholar 

  20. Flamme I, Frohlich T, von Reutern M, Kappel A, Damert A, Risau W (1997) HRF, a putative basic helix-loop-helix-PAS-domain transcription factor is closely related to hypoxia-inducible factor-1 alpha and developmentally expressed in blood vessels. Mech Dev 63:51–60

    PubMed  CAS  Google Scholar 

  21. Makino Y, Kanopka A, Wilson WJ, Tanaka H, Poellinger L (2002) Inhibitory PAS domain protein (IPAS) is a hypoxia-inducible splicing variant of the hypoxia-inducible factor-3alpha locus. J Biol Chem 277:32405–32408

    PubMed  CAS  Google Scholar 

  22. Crews ST (1998) Control of cell lineage-specific development and transcription by bHLH-PAS proteins. Genes Dev 12:607–620

    PubMed  CAS  Google Scholar 

  23. Chilov D, Camenisch G, Kvietikova I, Ziegler U, Gassmann M, Wenger RH (1999) Induction and nuclear translocation of hypoxia-inducible factor-1 (HIF-1): heterodimerization with ARNT is not necessary for nuclear accumulation of HIF-1alpha. J Cell Sci 112(Pt 8):1203–1212

    PubMed  CAS  Google Scholar 

  24. Iyer NV et al (1998) Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1 alpha. Genes Dev 12:149–162

    PubMed  CAS  Google Scholar 

  25. Ryan HE, Lo J, Johnson RS (1998) HIF-1 alpha is required for solid tumor formation and embryonic vascularization. Embo J 17:3005–3015

    PubMed  CAS  Google Scholar 

  26. Kotch LE, Iyer NV, Laughner E, Semenza GL (1999) Defective vascularization of HIF-1alpha-null embryos is not associated with VEGF deficiency but with mesenchymal cell death. Dev Biol 209:254–267

    PubMed  CAS  Google Scholar 

  27. Peng J, Zhang L, Drysdale L, Fong GH (2000) The transcription factor EPAS-1/hypoxia-inducible factor 2alpha plays an important role in vascular remodeling. Proc Natl Acad Sci U S A 97:8386–8391

    PubMed  CAS  Google Scholar 

  28. Tian H, Hammer RE, Matsumoto AM, Russell DW, McKnight SL (1998) The hypoxia-responsive transcription factor EPAS1 is essential for catecholamine homeostasis and protection against heart failure during embryonic development. Genes Dev 12:3320–3324

    PubMed  CAS  Google Scholar 

  29. Compernolle V et al (2002) Loss of HIF-2alpha and inhibition of VEGF impair fetal lung maturation, whereas treatment with VEGF prevents fatal respiratory distress in premature mice. Nat Med 8:702–710

    PubMed  CAS  Google Scholar 

  30. Yu AY et al (1999) Impaired physiological responses to chronic hypoxia in mice partially deficient for hypoxia-inducible factor 1alpha. J Clin Invest 103:691–696

    PubMed  CAS  Google Scholar 

  31. Shimoda LA, Manalo DJ, Sham JS, Semenza GL, Sylvester JT (2001) Partial HIF-1alpha deficiency impairs pulmonary arterial myocyte electrophysiological responses to hypoxia. Am J Physiol Lung Cell Mol Physiol 281:L202–L208

    Google Scholar 

  32. Ivan M et al (2001) HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science 292:464–468

    PubMed  CAS  Google Scholar 

  33. Jaakkola P et al (2001) Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 292:468–472

    PubMed  CAS  Google Scholar 

  34. Yu F, White SB, Zhao Q, Lee FS (2001) HIF-1alpha binding to VHL is regulated by stimulus-sensitive proline hydroxylation. Proc Natl Acad Sci U S A 98:9630–9635

    PubMed  CAS  Google Scholar 

  35. Masson N, Willam C, Maxwell PH, Pugh CW, Ratcliffe PJ (2001) Independent function of two destruction domains in hypoxia-inducible factor-alpha chains activated by prolyl hydroxylation. Embo J 20:5197–5206

    PubMed  CAS  Google Scholar 

  36. Maxwell PH et al (1999) The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-­dependent proteolysis. Nature 399:271–275

    PubMed  CAS  Google Scholar 

  37. Ohh M et al (2000) Ubiquitination of hypoxia-inducible factor requires direct binding to the beta-domain of the von Hippel-Lindau protein. Nat Cell Biol 2:423–427

    PubMed  CAS  Google Scholar 

  38. Tanimoto K, Makino Y, Pereira T, Poellinger L (2000) Mechanism of regulation of the hypoxia-inducible factor-1 alpha by the von Hippel-Lindau tumor suppressor protein. Embo J 19:4298–4309

    PubMed  CAS  Google Scholar 

  39. Bruick RK, McKnight SL (2001) A conserved family of prolyl-4-hydroxylases that modify HIF. Science 294: 1337–1340

    PubMed  CAS  Google Scholar 

  40. Epstein AC et al (2001) C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell 107:43–54

    PubMed  CAS  Google Scholar 

  41. Taylor MS (2001) Characterization and comparative analysis of the EGLN gene family. Gene 275:125–132

    PubMed  CAS  Google Scholar 

  42. Ivan M et al (2002) Biochemical purification and pharmacological inhibition of a mammalian prolyl hydroxylase acting on hypoxia-inducible factor. Proc Natl Acad Sci U S A 99: 13459–13464

    PubMed  CAS  Google Scholar 

  43. Berra E, Benizri E, Ginouves A, Volmat V, Roux D, Pouyssegur J (2003) HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1alpha in normoxia. EMBO J 22:4082–4090

    PubMed  CAS  Google Scholar 

  44. Huang J, Zhao Q, Mooney SM, Lee FS (2002) Sequence determinants in hypoxia-inducible factor-1alpha for hydroxylation by the prolyl hydroxylases PHD1, PHD2, and PHD3. J Biol Chem 277:39792–39800

    PubMed  CAS  Google Scholar 

  45. Metzen E et al (2003) Intracellular localisation of human HIF-1 alpha hydroxylases: implications for oxygen sensing. J Cell Sci 116:1319–1326

    PubMed  CAS  Google Scholar 

  46. Berra E, Richard DE, Gothie E, Pouyssegur J (2001) HIF-1-dependent transcriptional activity is required for oxygen-mediated HIF-1alpha degradation. FEBS Lett 491:85–90

    PubMed  CAS  Google Scholar 

  47. Lando D, Peet DJ, Gorman JJ, Whelan DA, Whitelaw ML, Bruick RK (2002) FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. Genes Dev 16:1466–1471

    PubMed  CAS  Google Scholar 

  48. Jeong JW et al (2002) Regulation and destabilization of HIF-1alpha by ARD1-mediated acetylation. Cell 111: 709–720

    PubMed  CAS  Google Scholar 

  49. Arnesen T et al (2005) Interaction between HIF-1 alpha (ODD) and hARD1 does not induce acetylation and destabilization of HIF-1 alpha. FEBS Lett 579:6428–6432

    PubMed  CAS  Google Scholar 

  50. Murray-Rust TA, Oldham NJ, Hewitson KS, Schofield CJ (2006) Purified recombinant hARD1 does not catalyse acetylation of Lys532 of HIF-1alpha fragments in vitro. FEBS Lett 580:1911–1918

    PubMed  CAS  Google Scholar 

  51. Chang CC et al (2006) Effect of connective tissue growth factor on hypoxia-inducible factor 1alpha degradation and tumor angiogenesis. J Natl Cancer Inst 98:984–995

    PubMed  CAS  Google Scholar 

  52. Kim SH, Jeong JW, Park JA, Lee JW, Seo JH, Jung BK, Bae MK, Kim KW (2007) Regulation of the HIF-1alpha stability by histone deacetylases. Oncol Rep 17:647–651

    PubMed  CAS  Google Scholar 

  53. Qian DZ, Kachhap SK, Collis SJ, Verheul HM, Carducci MA, Atadja P, Pili R (2006) Class II histone deacetylases are associated with VHL-independent regulation of hypoxia-inducible factor 1 alpha. Cancer Res 66:8814–8821

    PubMed  CAS  Google Scholar 

  54. Kato H, Tamamizu-Kato S, Shibasaki F (2004) Histone deacetylase 7 associates with hypoxia-inducible factor 1alpha and increases transcriptional activity. J Biol Chem 279:41966–41974

    PubMed  CAS  Google Scholar 

  55. Kong X, Lin Z, Liang D, Fath D, Sang N, Caro J (2006) Histone deacetylase inhibitors induce VHL and ubiquitin-independent proteasomal degradation of hypoxia-inducible factor 1alpha. Mol Cell Biol 26:2019–2028

    PubMed  CAS  Google Scholar 

  56. Yoo YG, Na TY, Seo HW, Seong JK, Park CK, Shin YK, Lee MO (2008) Hepatitis B virus X protein induces the expression of MTA1 and HDAC1, which enhances hypoxia signaling in hepatocellular carcinoma cells. Oncogene 27: 3405–3413

    PubMed  CAS  Google Scholar 

  57. Yoo YG, Kong G, Lee MO (2006) Metastasis-associated protein 1 enhances stability of hypoxia-inducible factor-1alpha protein by recruiting histone deacetylase 1. EMBO J 25:1231–1241

    PubMed  CAS  Google Scholar 

  58. Ellis L, Hammers H, Pili R (2009) Targeting tumor angiogenesis with histone deacetylase inhibitors. Cancer Lett 280:145–53

    Google Scholar 

  59. Sodhi A, Montaner S, Patel V, Zohar M, Bais C, Mesri EA, Gutkind JS (2000) The Kaposi’s sarcoma-associated herpes virus G protein-coupled receptor up-regulates vascular endothelial growth factor expression and secretion through mitogen-activated protein kinase and p38 pathways acting on hypoxia-inducible factor 1a. Cancer Res 60: 4873–4880

    PubMed  CAS  Google Scholar 

  60. Richard DE, Berra E, Gothie E, Roux D, Pouyssegur J (1999) p42/p44 mitogen-activated protein kinases phosphorylate hypoxia-inducible factor 1alpha (HIF-1alpha) and enhance the transcriptional activity of HIF-1. J Biol Chem 274:32631–32637

    PubMed  CAS  Google Scholar 

  61. Mylonis I et al (2006) Identification of MAPK phosphorylation sites and their role in the localization and activity of hypoxia-inducible factor-1alpha. J Biol Chem 281:33095–33106

    PubMed  CAS  Google Scholar 

  62. Mylonis I, Chachami G, Paraskeva E, Simos G (2008) Atypical CRM1-dependent nuclear export signal mediates regulation of hypoxia-inducible factor-1alpha by MAPK.J Biol Chem 283:27620–27627

    PubMed  CAS  Google Scholar 

  63. Suzuki H, Tomida A, Tsuruo T (2001) Dephosphorylated hypoxia-inducible factor 1alpha as a mediator ofp53-dependent apoptosis during hypoxia. Oncogene 20:5779–5788

    PubMed  CAS  Google Scholar 

  64. Flugel D, Gorlach A, Michiels C, Kietzmann T (2007) Glycogen synthase kinase 3 phosphorylates hypoxia-inducible factor 1alpha and mediates its destabilization in a VHL-independent manner. Mol Cell Biol 27:3253–3265

    PubMed  Google Scholar 

  65. Yasinska IM, Sumbayev VV (2003) S-nitrosation of Cys-800 of HIF-1alpha protein activates its interaction with p300 and stimulates its transcriptional activity. FEBS Lett 549:105–109

    PubMed  CAS  Google Scholar 

  66. Li F et al (2007) Regulation of HIF-1alpha stability through S-nitrosylation. Mol Cell 26:63–74

    PubMed  Google Scholar 

  67. Comerford KM, Leonard MO, Karhausen J, Carey R, Colgan SP, Taylor CT (2003) Small ubiquitin-related modifier-1 modification mediates resolution of CREB-dependent responses to hypoxia. Proc Natl Acad Sci U S A 100:986–991

    PubMed  CAS  Google Scholar 

  68. Bae SH, Jeong JW, Park JA, Kim SH, Bae MK, Choi SJ, Kim KW (2004) Sumoylation increases HIF-1alpha stability and its transcriptional activity. Biochem Biophys Res Commun 324:394–400

    PubMed  CAS  Google Scholar 

  69. Carbia-Nagashima A, Gerez J, Perez-Castro C, Paez-Pereda M, Silberstein S, Stalla GK, Holsboer F, Arzt E (2007) RSUME, a small RWD-containing protein, enhances SUMO conjugation and stabilizes HIF-1alpha during hypoxia. Cell 131:309–323

    PubMed  CAS  Google Scholar 

  70. Berta MA, Mazure N, Hattab M, Pouyssegur J, Brahimi-Horn MC (2007) SUMOylation of hypoxia-inducible factor-1alpha reduces its transcriptional activity. Biochem Biophys Res Commun 360:646–652

    PubMed  CAS  Google Scholar 

  71. Cheng J, Kang X, Zhang S, Yeh ET (2007) SUMO-specific protease 1 is essential for stabilization of HIF1alpha during hypoxia. Cell 131:584–595

    PubMed  CAS  Google Scholar 

  72. Jungermann K, Kietzmann T (1996) Zonation of parenchymal and nonparenchymal metabolism in liver. Annu Rev Nutr 16:179–203

    PubMed  CAS  Google Scholar 

  73. Roth U, Curth K, Unterman TG, Kietzmann T (2004) The transcription factors HIF-1 and HNF-4 and the coactivator p300 are involved in insulin-regulated glucokinase gene expression via the phosphatidylinositol 3-kinase/protein kinase B pathway. J Biol Chem 279:2623–2631

    PubMed  CAS  Google Scholar 

  74. Stroka DM, Burkhardt T, Desbaillets I, Wenger RH, Neil DA, Bauer C, Gassmann M, Candinas D (2001) HIF-1 is expressed in normoxic tissue and displays an organ-­specific regulation under systemic hypoxia. Faseb J 15: 2445–2453

    PubMed  CAS  Google Scholar 

  75. Wiesener MS et al (2003) Widespread hypoxia-inducible expression of HIF-2alpha in distinct cell populations of different organs. Faseb J 17:271–273

    PubMed  CAS  Google Scholar 

  76. Hu CJ, Wang LY, Chodosh LA, Keith B, Simon MC (2003) Differential roles of hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha in hypoxic gene regulation. Mol Cell Biol 23:9361–9374

    PubMed  CAS  Google Scholar 

  77. Rankin EB et al (2007) Hypoxia-inducible factor-2 (HIF-2) regulates hepatic erythropoietin in vivo. J Clin Invest 117:1068–1077

    PubMed  CAS  Google Scholar 

  78. Gumucio JJ, Miller DL (1981) Functional implications of liver cell heterogeneity. Gastroenterology 80:393–403

    PubMed  CAS  Google Scholar 

  79. Alchera E et al (2008) Adenosine-dependent activation of hypoxia-inducible factor-1 induces late preconditioning in liver cells. Hepatology 48:230–239

    PubMed  CAS  Google Scholar 

  80. Plock J et al (2007) Activation of non-ischemic, hypoxia-inducible signalling pathways up-regulate cytoprotective genes in the murine liver. J Hepatol 47:538–545

    PubMed  CAS  Google Scholar 

  81. Rosmorduc O, Wendum D, Corpechot C, Galy B, Sebbagh N, Raleigh J, Housset C, Poupon R (1999) Hepatocellular hypoxia-induced vascular endothelial growth factor expression and angiogenesis in experimental biliary cirrhosis. Am J Pathol 155:1065–1073

    PubMed  CAS  Google Scholar 

  82. Corpechot C, Barbu V, Wendum D, Chignard N, Housset C, Poupon R, Rosmorduc O (2002) Hepatocyte growth factor and c-Met inhibition by hepatic cell hypoxia: a potential mechanism for liver regeneration failure in experimental cirrhosis. Am J Pathol 160:613–620

    PubMed  CAS  Google Scholar 

  83. Corpechot C, Barbu V, Wendum D, Kinnman N, Rey C, Poupon R, Housset C, Rosmorduc O (2002) Hypoxia-induced VEGF and collagen I expressions are associated with angiogenesis and fibrogenesis in experimental cirrhosis. Hepatology 35:1010–1021

    PubMed  CAS  Google Scholar 

  84. Aebersold DM, Burri P, Beer KT, Laissue J, Djonov V, Greiner RH, Semenza GL (2001) Expression of hypoxia-inducible factor-1alpha: a novel predictive and prognostic parameter in the radiotherapy of oropharyngeal cancer. Cancer Res 61:2911–2916

    PubMed  CAS  Google Scholar 

  85. Kung AL, Wang S, Klco JM, Kaelin WG, Livingston DM (2000) Suppression of tumor growth through disruption of hypoxia-inducible transcription. Nat Med 6:1335–1340

    PubMed  CAS  Google Scholar 

  86. Nordsmark M, Bentzen SM, Overgaard J (1994) Measurement of human tumour oxygenation status by a polarographic needle electrode. An analysis of inter- and intratumour heterogeneity. Acta Oncol 33:383–389

    CAS  Google Scholar 

  87. Nordsmark M et al (2003) Measurements of hypoxia using pimonidazole and polarographic oxygen-sensitive electrodes in human cervix carcinomas. Radiother Oncol 67:35–44

    PubMed  Google Scholar 

  88. Pennacchietti S, Michieli P, Galluzzo M, Mazzone M, Giordano S, Comoglio PM (2003) Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene. Cancer Cell 3:347–361

    PubMed  Google Scholar 

  89. Staller P, Sulitkova J, Lisztwan J, Moch H, Oakeley EJ, Krek W (2003) Chemokine receptor CXCR4 downregulated by von Hippel-Lindau tumour suppressor pVHL. Nature 425:307–311

    PubMed  CAS  Google Scholar 

  90. Comerford KM, Wallace TJ, Karhausen J, Louis NA, Montalto MC, Colgan SP (2002) Hypoxia-inducible factor-1-dependent regulation of the multidrug resistance (MDR1) gene. Cancer Res 62:3387–3394

    PubMed  CAS  Google Scholar 

  91. Poon RT, Ng IO, Lau C, Zhu LX, Yu WC, Lo CM, Fan ST, Wong J (2001) Serum vascular endothelial growth factor predicts venous invasion in hepatocellular carcinoma: a prospective study. Ann Surg 233:227–235

    PubMed  CAS  Google Scholar 

  92. Yasuda S et al (2004) Hexokinase II and VEGF expression in liver tumors: correlation with hypoxia-inducible factor 1 alpha and its significance. J Hepatol 40:117–123

    PubMed  CAS  Google Scholar 

  93. Seagroves TN, Ryan HE, Lu H, Wouters BG, Knapp M, Thibault P, Laderoute K, Johnson RS (2001) Transcription factor HIF-1 is a necessary mediator of the pasteur effect in mammalian cells. Mol Cell Biol 21:3436–3444

    PubMed  CAS  Google Scholar 

  94. Jiang BH, Agani F, Passaniti A, Semenza GL (1997) V-SRC induces expression of hypoxia-inducible factor 1 (HIF-1) and transcription of genes encoding vascular endothelial growth factor and enolase 1: involvement of HIF-1 in tumor progression. Cancer Res 57:5328–5335

    PubMed  CAS  Google Scholar 

  95. Ravi R et al (2000) Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha. Genes Dev 14:34–44

    PubMed  CAS  Google Scholar 

  96. Zundel W et al (2000) Loss of PTEN facilitates HIF-1-mediated gene expression. Genes Dev 14:391–396

    PubMed  CAS  Google Scholar 

  97. Haase VH, Glickman JN, Socolovsky M, Jaenisch R (2001) Vascular tumors in livers with targeted inactivation of the von Hippel-Lindau tumor suppressor. Proc Natl Acad Sci U S A 98:1583–1588

    PubMed  CAS  Google Scholar 

  98. Rankin EB, Higgins DF, Walisser JA, Johnson RS, Bradfield CA, Haase VH (2005) Inactivation of the arylhydrocarbon receptor nuclear translocator (Arnt) suppresses von Hippel-Lindau disease-associated vascular tumors in mice. Mol Cell Biol 25:3163–3172

    PubMed  CAS  Google Scholar 

  99. Rankin EB et al (2008) Hypoxia-inducible factor-2 regulates vascular tumorigenesis in mice. Oncogene 27:5354–5358

    PubMed  CAS  Google Scholar 

  100. Michalopoulos GK, DeFrances MC (1997) Liver regeneration. Science 276:60–66

    PubMed  CAS  Google Scholar 

  101. Su AI, Guidotti LG, Pezacki JP, Chisari FV, Schultz PG (2002) Gene expression during the priming phase of liver regeneration after partial hepatectomy in mice. Proc Natl Acad Sci U S A 99:11181–11186

    PubMed  CAS  Google Scholar 

  102. Schmeding M, Boas-Knoop S, Lippert S, Ruehl M, Somasundaram R, Dagdelen T, Neuhaus P, Neumann UP (2008) Erythropoietin promotes hepatic regeneration after extended liver resection in rats. J Gastroenterol Hepatol 23:1125–1131

    PubMed  CAS  Google Scholar 

  103. Conrad PW, Freeman TL, Beitner-Johnson D, Millhorn DE (1999) EPAS1 trans-activation during hypoxia requires p42/p44 MAPK. J Biol Chem 274:33709–33713

    PubMed  CAS  Google Scholar 

  104. Conrad PW, Rust RT, Han J, Millhorn DE,Beitner-Johnson D (1999) Selective activation of p38alpha and p38gamma by hypoxia. Role in regulation of cyclin D1 by hypoxia in PC12 cells. J Biol Chem 274:23570–23576

    PubMed  CAS  Google Scholar 

  105. Hirota K, Semenza GL (2001) Rac1 activity is required for the activation of hypoxia-inducible factor 1. J Biol Chem 276:21166–21172

    PubMed  CAS  Google Scholar 

  106. Aragones J et al (2001) Evidence for the involvement of diacylglycerol kinase in the activation of hypoxia-inducible transcription factor 1 by low oxygen tension. J Biol Chem 276:10548–10555

    PubMed  CAS  Google Scholar 

  107. Ausserer WA, Bourrat-Floeck B, Green CJ, Laderoute KR, Sutherland RM (1994) Regulation of c-jun expression during hypoxic and low-glucose stress. Mol Cell Biol 14:5032–5042

    PubMed  CAS  Google Scholar 

  108. Figueroa YG, Chan AK, Ibrahim R, Tang Y, Burow ME, Alam J, Scandurro AB, Beckman BS (2002) NF-kappaB plays a key role in hypoxia-inducible factor-1-regulated erythropoietin gene expression. Exp Hematol 30:1419–1427

    PubMed  CAS  Google Scholar 

  109. Yan SF et al (1999) Hypoxia-associated induction of early growth response-1 gene expression. J Biol Chem 274: 15030–15040

    PubMed  CAS  Google Scholar 

  110. Levy AP, Levy NS, Goldberg MA (1996) Post-transcriptional regulation of vascular endothelial growth factor by hypoxia. J Biol Chem 271:2746–2753

    PubMed  CAS  Google Scholar 

  111. Shima DT, Deutsch U, D’Amore PA (1995) Hypoxic induction of vascular endothelial growth factor (VEGF) in human epithelial cells is mediated by increases in mRNA stability. FEBS Lett 370:203–208

    PubMed  CAS  Google Scholar 

  112. Liu LX et al (2002) Stabilization of vascular endothelial growth factor mRNA by hypoxia-inducible factor 1. Biochem Biophys Res Commun 291:908–914

    PubMed  CAS  Google Scholar 

  113. Mukhopadhyay CK, Mazumder B, Fox PL (2000) Role of hypoxia-inducible factor-1 in transcriptional activation of ceruloplasmin by iron deficiency. J Biol Chem 275: 21048–21054

    PubMed  CAS  Google Scholar 

  114. Rolfs A, Kvietikova I, Gassmann M, Wenger RH (1997) Oxygen-regulated transferrin expression is mediated by hypoxia-inducible factor-1. J Biol Chem 272: 20055–20062

    PubMed  CAS  Google Scholar 

  115. Tacchini L, Fusar Poli D, Bernelli-Zazzera A, Cairo G (2002) Transferrin receptor gene expression and transferrin-bound iron uptake are increased during postischemic rat liver reperfusion. Hepatology 36:103–111

    PubMed  CAS  Google Scholar 

  116. Lok CN, Ponka P (1999) Identification of a hypoxia response element in the transferrin receptor gene. J Biol Chem 274:24147–24152

    PubMed  CAS  Google Scholar 

  117. Liu YL, Ang SO, Weigent DA, Prchal JT, Bloomer JR (2004) Regulation of ferrochelatase gene expression by hypoxia. Life Sci 75:2035–2043

    PubMed  CAS  Google Scholar 

  118. Liu Y, Cox SR, Morita T, Kourembanas S (1995) Hypoxia regulates vascular endothelial growth factor gene expression in endothelial cells. Identification of a 5' enhancer. Circ Res 77:638–643

    PubMed  CAS  Google Scholar 

  119. Forsythe JA, Jiang BH, Iyer NV, Agani F, Leung SW, Koos RD, Semenza GL (1996) Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol 16:4604–4613

    PubMed  CAS  Google Scholar 

  120. Levy AP, Levy NS, Wegner S, Goldberg MA (1995) Transcriptional regulation of the rat vascular endothelial growth factor gene by hypoxia. J Biol Chem 270: 13333–13340

    PubMed  CAS  Google Scholar 

  121. Gerber HP, Condorelli F, Park J, Ferrara N (1997) Differential transcriptional regulation of the two vascular endothelial growth factor receptor genes. Flt-1, but not Flk-1/KDR, is up-regulated by hypoxia. J Biol Chem 272:23659–23667

    PubMed  CAS  Google Scholar 

  122. LeCouter J et al (2001) Identification of an angiogenic mitogen selective for endocrine gland endothelium. Nature 412:877–884

    PubMed  CAS  Google Scholar 

  123. Eckhart AD, Yang N, Xin X, Faber JE (1997) Charac­terization of the alpha1B-adrenergic receptor gene promoter region and hypoxia regulatory elements in vascular smooth muscle. Proc Natl Acad Sci U S A 94:9487–9492

    PubMed  CAS  Google Scholar 

  124. Lee PJ, Jiang BH, Chin BY, Iyer NV, Alam J, Semenza GL, Choi AM (1997) Hypoxia-inducible factor-1 mediates transcriptional activation of the heme oxygenase-1 gene in response to hypoxia. J Biol Chem 272:5375–5381

    PubMed  CAS  Google Scholar 

  125. Melillo G, Musso T, Sica A, Taylor LS, Cox GW, Varesio L (1995) A hypoxia-responsive element mediates a novel pathway of activation of the inducible nitric oxide synthase promoter. J Exp Med 182:1683–1693

    PubMed  CAS  Google Scholar 

  126. Hu J, Discher DJ, Bishopric NH, Webster KA (1998) Hypoxia regulates expression of the endothelin-1 gene through a proximal hypoxia-inducible factor-1 binding site on the antisense strand. Biochem Biophys Res Commun 245:894–899

    PubMed  CAS  Google Scholar 

  127. Chen YF, Durand J, Claycomb WC (1997) Hypoxia stimulates atrial natriuretic peptide gene expression in cultured atrial cardiocytes. Hypertension 29:75–82

    PubMed  CAS  Google Scholar 

  128. Kietzmann T, Roth U, Jungermann K (1999) Induction of the plasminogen activator inhibitor-1 gene expression by mild hypoxia via a hypoxia response element binding the hypoxia-inducible factor-1 in rat hepatocytes. Blood 94: 4177–4185

    PubMed  CAS  Google Scholar 

  129. Nguyen SV, Claycomb WC (1999) Hypoxia regulates the expression of the adrenomedullin and HIF-1 genes in cultured HL-1 cardiomyocytes. Biochem Biophys Res Commun 265:382–386

    PubMed  CAS  Google Scholar 

  130. Cormier-Regard S, Nguyen SV, Claycomb WC (1998) Adrenomedullin gene expression is developmentally regulated and induced by hypoxia in rat ventricular cardiac myocytes. J Biol Chem 273:17787–17792

    PubMed  CAS  Google Scholar 

  131. Wykoff CC, Pugh CW, Maxwell PH, Harris AL, Ratcliffe PJ (2000) Identification of novel hypoxia dependent and independent target genes of the von Hippel-Lindau (VHL) tumour suppressor by mRNA differential expression profiling. Oncogene 19:6297–6305

    PubMed  CAS  Google Scholar 

  132. Saed GM, Collins KL, Diamond MP (2002) Transforming growth factors beta1, beta2 and beta3 and their receptors are differentially expressed in human peritoneal fibroblasts in response to hypoxia. Am J Reprod Immunol 48: 387–393

    PubMed  Google Scholar 

  133. Ambrosini G, Nath AK, Sierra-Honigmann MR, Flores-Riveros J (2002) Transcriptional activation of the human leptin gene in response to hypoxia. Involvement of hypoxia-inducible factor 1. J Biol Chem 277:34601–34609

    PubMed  CAS  Google Scholar 

  134. Grosfeld A, Andre J, Hauguel-De Mouzon S, Berra E, Pouyssegur J, Guerre-Millo M (2002) Hypoxia-inducible factor 1 transactivates the human leptin gene promoter.J Biol Chem 277:42953–42957

    PubMed  CAS  Google Scholar 

  135. Sanchez-Elsner T, Botella LM, Velasco B, Langa C, Bernabeu C (2002) Endoglin expression is regulated by transcriptional cooperation between the hypoxia and transforming growth factor-beta pathways. J Biol Chem 277: 43799–43808

    PubMed  CAS  Google Scholar 

  136. Shimo T, Kubota S, Kondo S, Nakanishi T, Sasaki A, Mese H, Matsumura T, Takigawa M (2001) Connective tissue growth factor as a major angiogenic agent that is induced by hypoxia in a human breast cancer cell line. Cancer Lett 174:57–64

    PubMed  CAS  Google Scholar 

  137. Takahashi Y, Takahashi S, Shiga Y, Yoshimi T, Miura T (2000) Hypoxic induction of prolyl 4-hydroxylase alpha (I) in cultured cells. J Biol Chem 275:14139–14146

    PubMed  CAS  Google Scholar 

  138. Krishnamachary B et al (2003) Regulation of colon carcinoma cell invasion by hypoxia-inducible factor 1. Cancer Res 63:1138–1143

    PubMed  CAS  Google Scholar 

  139. Ebert BL, Firth JD, Ratcliffe PJ (1995) Hypoxia and mitochondrial inhibitors regulate expression of glucose transporter-1 via distinct Cis-acting sequences. J Biol Chem 270:29083–29089

    PubMed  CAS  Google Scholar 

  140. O’Rourke JF, Pugh CW, Bartlett SM, Ratcliffe PJ (1996) Identification of hypoxically inducible mRNAs in HeLa cells using differential-display PCR. Role of hypoxia-inducible factor-1. Eur J Biochem 241:403–410

    PubMed  Google Scholar 

  141. Semenza GL, Jiang BH, Leung SW, Passantino R, Concordet JP, Maire P, Giallongo A (1996) Hypoxia response elements in the aldolase A, enolase 1, and lactate dehydrogenase A gene promoters contain essential binding sites for hypoxia-inducible factor 1. J Biol Chem 271: 32529–32537

    PubMed  CAS  Google Scholar 

  142. Semenza GL, Roth PH, Fang HM, Wang GL (1994) Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1. J Biol Chem 269:23757–23763

    PubMed  CAS  Google Scholar 

  143. Firth JD, Ebert BL, Ratcliffe PJ (1995) Hypoxic regulation of lactate dehydrogenase A. Interaction between hypoxia-inducible factor 1 and cAMP response elements. J Biol Chem 270:21021–21027

    PubMed  CAS  Google Scholar 

  144. Firth JD, Ebert BL, Pugh CW, Ratcliffe PJ (1994) Oxygen-regulated control elements in the phosphoglycerate kinase 1 and lactate dehydrogenase A genes: similarities with the erythropoietin 3' enhancer. Proc Natl Acad Sci U S A 91:6496–6500

    PubMed  CAS  Google Scholar 

  145. Graven KK, Yu Q, Pan D, Roncarati JS, Farber HW (1999) Identification of an oxygen responsive enhancer element in the glyceraldehyde-3-phosphate dehydrogenase gene. Biochim Biophys Acta 1447:208–218

    PubMed  CAS  Google Scholar 

  146. Yoon DY, Buchler P, Saarikoski ST, Hines OJ, Reber HA, Hankinson O (2001) Identification of genes differentially induced by hypoxia in pancreatic cancer cells. Biochem Biophys Res Commun 288:882–886

    PubMed  CAS  Google Scholar 

  147. Minchenko A, Leshchinsky I, Opentanova I, Sang N, Srinivas V, Armstead V, Caro J (2002) Hypoxia-inducible factor-1-mediated expression of the 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase-3 (PFKFB3) gene. Its possible role in the Warburg effect. J Biol Chem 277:6183–6187

    PubMed  CAS  Google Scholar 

  148. Minchenko O, Opentanova I, Minchenko D, Ogura T, Esumi H (2004) Hypoxia induces transcription of 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase-4 gene via hypoxia-inducible factor-1alpha activation. FEBS Lett 576:14–20

    PubMed  CAS  Google Scholar 

  149. Gess B, Hofbauer KH, Deutzmann R, Kurtz A (2004) Hypoxia up-regulates triosephosphate isomerase expression via a HIF-dependent pathway. Pflugers Arch 448:175–180

    PubMed  CAS  Google Scholar 

  150. Roth U, Jungermann K, Kietzmann T (2004) Modulation of glucokinase expression by hypoxia-inducible factor 1 and upstream stimulatory factor 2 in primary rat hepatocytes. Biol Chem 385:239–247

    PubMed  CAS  Google Scholar 

  151. Choi JH, Park MJ, Kim KW, Choi YH, Park SH, An WG, Yang US, Cheong J (2005) Molecular mechanism of hypoxia-mediated hepatic gluconeogenesis by transcriptional regulation. FEBS Lett 579:2795–2801

    PubMed  CAS  Google Scholar 

  152. Wykoff CC et al (2000) Hypoxia-inducible expression of tumor-associated carbonic anhydrases. Cancer Res 60: 7075–7083

    PubMed  CAS  Google Scholar 

  153. Shimoda LA, Fallon M, Pisarcik S, Wang J, Semenza GL (2006) HIF-1 regulates hypoxic induction of NHE1 expression and alkalinization of intracellular pH in pulmonary arterial myocytes. Am J Physiol Lung Cell Mol Physiol 291:L941–L949

    Google Scholar 

  154. Tazuke SI et al (1998) Hypoxia stimulates insulin-like growth factor binding protein 1 (IGFBP-1) gene expression in HepG2 cells: a possible model for IGFBP-1 expression in fetal hypoxia. Proc Natl Acad Sci U S A 95:10188–10193

    PubMed  CAS  Google Scholar 

  155. Feldser D, Agani F, Iyer NV, Pak B, Ferreira G, Semenza GL (1999) Reciprocal positive regulation of hypoxia-inducible factor 1alpha and insulin-like growth factor 2. Cancer Res 59:3915–3918

    PubMed  CAS  Google Scholar 

  156. Carmeliet P et al (1998) Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature 394:485–490

    PubMed  CAS  Google Scholar 

  157. Nishi H, Nakada T, Kyo S, Inoue M, Shay JW, Isaka K (2004) Hypoxia-inducible factor 1 mediates upregulation of telomerase (hTERT). Mol Cell Biol 24:6076–6083

    PubMed  CAS  Google Scholar 

  158. Li J, Zhang X, Sejas DP, Bagby GC, Pang Q (2004) Hypoxia-induced nucleophosmin protects cell death through inhibition of p53. J Biol Chem 279:41275–41279

    PubMed  CAS  Google Scholar 

  159. Bruick RK (2000) Expression of the gene encoding the proapoptotic Nip3 protein is induced by hypoxia. Proc Natl Acad Sci U S A 97:9082–9087

    PubMed  CAS  Google Scholar 

  160. Erler JT et al (2004) Hypoxia-mediated down-regulation of Bid and Bax in tumors occurs via hypoxia-inducible factor 1-dependent and -independent mechanisms and contributes to drug resistance. Mol Cell Biol 24:2875–2889

    PubMed  CAS  Google Scholar 

  161. Sowter HM, Ratcliffe PJ, Watson P, Greenberg AH, Harris AL (2001) HIF-1-dependent regulation of hypoxic induction of the cell death factors BNIP3 and NIX in human tumors. Cancer Res 61:6669–6673

    PubMed  CAS  Google Scholar 

  162. Shoshani T et al (2002) Identification of a novel hypoxia-inducible factor 1-responsive gene, RTP801, involved in apoptosis. Mol Cell Biol 22:2283–2293

    PubMed  CAS  Google Scholar 

  163. Kim JY, Ahn HJ, Ryu JH, Suk K, Park JH (2004) BH3-only protein Noxa is a mediator of hypoxic cell death induced by hypoxia-inducible factor 1alpha. J Exp Med 199:113–124

    PubMed  CAS  Google Scholar 

  164. Lee MJ, Kim JY, Suk K, Park JH (2004) Identification of the hypoxia-inducible factor 1 alpha-responsive HGTD-P gene as a mediator in the mitochondrial apoptotic pathway. Mol Cell Biol 24:3918–3927

    PubMed  CAS  Google Scholar 

  165. Piret JP, Minet E, Cosse JP, Ninane N, Debacq C, Raes M, Michiels C (2005) Hypoxia-inducible factor-1-dependent overexpression of myeloid cell factor-1 protects hypoxic cells against tert-butyl hydroperoxide-induced apoptosis. J Biol Chem 280:9336–9344

    PubMed  CAS  Google Scholar 

  166. Liu XH, Yu EZ, Li YY, Kagan E (2006) HIF-1alpha has an anti-apoptotic effect in human airway epithelium that is mediated via Mcl-1 gene expression. J Cell Biochem 97: 755–765

    PubMed  CAS  Google Scholar 

  167. Peng XH, Karna P, Cao Z, Jiang BH, Zhou M, Yang L (2006) Cross-talk between epidermal growth factor receptor and hypoxia-inducible factor-1alpha signal pathways increases resistance to apoptosis by up-regulating survivin gene expression. J Biol Chem 281:25903–25914

    PubMed  CAS  Google Scholar 

  168. Bazan NG, Lukiw WJ (2002) Cyclooxygenase-2 and presenilin-1 gene expression induced by interleukin-1beta and amyloid beta 42 peptide is potentiated by hypoxia in primary human neural cells. J Biol Chem 277:30359–30367

    PubMed  CAS  Google Scholar 

  169. Kong T, Eltzschig HK, Karhausen J, Colgan SP, Shelley CS (2004) Leukocyte adhesion during hypoxia is mediated by HIF-1-dependent induction of beta2 integrin gene expression. Proc Natl Acad Sci U S A 101:10440–10445

    PubMed  CAS  Google Scholar 

  170. Mastyugin V, Mezentsev A, Zhang WX, Ashkar S, Dunn MW, Laniado-Schwartzman M (2004) Promoter activity and regulation of the corneal CYP4B1 gene by hypoxia.J Cell Biochem 91:1218–1238

    PubMed  CAS  Google Scholar 

  171. Makino Y et al (2003) Hypoxia-inducible factor regulates survival of antigen receptor-driven T cells. J Immunol 171: 6534–6540

    PubMed  CAS  Google Scholar 

  172. Kong T, Westerman KA, Faigle M, Eltzschig HK, Colgan SP (2006) HIF-dependent induction of adenosine A2B receptor in hypoxia. Faseb J 20:2242–2250

    PubMed  CAS  Google Scholar 

  173. Baugh JA, Gantier M, Li L, Byrne A, Buckley A, Donnelly SC (2006) Dual regulation of macrophage migration inhibitory factor (MIF) expression in hypoxia by CREB and HIF-1. Biochem Biophys Res Commun 347:895–903

    PubMed  CAS  Google Scholar 

  174. Estes SD, Stoler DL, Anderson GR (1995) Anoxic induction of a sarcoma virus-related VL30 retrotransposon is mediated by a cis-acting element which binds hypoxia-inducible factor 1 and an anoxia-inducible factor. J Virol 69:6335–6341

    PubMed  CAS  Google Scholar 

  175. Furuta GT, Turner JR, Taylor CT, Hershberg RM, Comerford K, Narravula S, Podolsky DK, Colgan SP (2001) Hypoxia-inducible factor 1-dependent induction of intestinal trefoil factor protects barrier function during hypoxia. J Exp Med 193:1027–1034

    PubMed  CAS  Google Scholar 

  176. Metzen E, Stiehl DP, Doege K, Marxsen JH, Hellwig-Burgel T, Jelkmann W (2005) Regulation of the prolyl hydroxylase domain protein 2 (phd2/egln-1) gene: identification of a functional hypoxia-responsive element. Biochem J 387: 711–717

    PubMed  CAS  Google Scholar 

  177. Pescador N, Cuevas Y, Naranjo S, Alcaide M, Villar D, Landazuri MO, Del Peso L (2005) Identification of a functional hypoxia-responsive element that regulates the expression of the egl nine homologue 3 (egln3/phd3) gene. Biochem J 390:189–197

    PubMed  CAS  Google Scholar 

  178. Zhou D, Salnikow K, Costa M (1998) Cap43, a novel gene specifically induced by Ni2+ compounds. Cancer Res 58: 2182–2189

    PubMed  CAS  Google Scholar 

  179. Ceradini DJ et al (2004) Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med 10:858–864

    PubMed  CAS  Google Scholar 

  180. Wagner KD, Wagner N, Wellmann S, Schley G, Bondke A, Theres H, Scholz H (2003) Oxygen-regulated expression of the Wilms’ tumor suppressor Wt1 involves hypoxia-inducible factor-1 (HIF-1). Faseb J 17:1364–1366

    PubMed  CAS  Google Scholar 

  181. Schioppa T et al (2003) Regulation of the chemokine receptor CXCR4 by hypoxia. J Exp Med 198:1391–1402

    PubMed  CAS  Google Scholar 

  182. Krishnamurthy P et al (2004) The stem cell marker Bcrp/ABCG2 enhances hypoxic cell survival through interactions with heme. J Biol Chem 279:24218–24225

    PubMed  CAS  Google Scholar 

  183. Ivanova AV, Ivanov SV, Danilkovitch-Miagkova A, Lerman MI (2001) Regulation of STRA13 by the von Hippel-Lindau tumor suppressor protein, hypoxia, and the UBC9/ubiquitin proteasome degradation pathway. J Biol Chem 276:15306–15315

    PubMed  CAS  Google Scholar 

  184. Miyazaki K, Kawamoto T, Tanimoto K, Nishiyama M, Honda H, Kato Y (2002) Identification of functional hypoxia response elements in the promoter region of the DEC1 and DEC2 genes. J Biol Chem 277:47014–47021

    PubMed  CAS  Google Scholar 

  185. Oikawa M, Abe M, Kurosawa H, Hida W, Shirato K, Sato Y (2001) Hypoxia induces transcription factor ETS-1 via the activity of hypoxia-inducible factor-1. Biochem Biophys Res Commun 289:39–43

    PubMed  CAS  Google Scholar 

  186. Choi JW, Park SC, Kang GH, Liu JO, Youn HD (2004) Nur77 activated by hypoxia-inducible factor-1alpha overproduces proopiomelanocortin in von Hippel-Lindau-mutated renal cell carcinoma. Cancer Res 64:35–39

    PubMed  CAS  Google Scholar 

  187. Bhattacharya S, Michels CL, Leung MK, Arany ZP, Kung AL, Livingston DM (1999) Functional role of p35srj, a novel p300/CBP binding protein, during transactivation by HIF-1. Genes Dev 13:64–75

    PubMed  CAS  Google Scholar 

  188. Yoshida D, Kim K, Noha M, Teramoto A (2006) Hypoxia inducible factor 1-alpha regulates of platelet derived growth factor-B in human glioblastoma cells. J Neurooncol 76: 13–21

    PubMed  CAS  Google Scholar 

  189. Paris S, Denis H, Delaive E, Dieu M, Dumont V, Ninane N, Raes M, Michiels C (2005) Up-regulation of 94-kDa glucose-regulated protein by hypoxia-inducible factor-1 in human endothelial cells in response to hypoxia. FEBS Lett 579:105–114

    PubMed  CAS  Google Scholar 

  190. McMahon S, Grondin F, McDonald PP, Richard DE, Dubois CM (2005) Hypoxia-enhanced expression of the proprotein convertase furin is mediated by hypoxia-inducible factor-1: impact on the bioactivation of proproteins. J Biol Chem 280:6561–6569

    PubMed  CAS  Google Scholar 

  191. Liu M, Alkayed NJ (2005) Hypoxic preconditioning and tolerance via hypoxia inducible factor (HIF) 1alpha-linked induction of P450 2C11 epoxygenase in astrocytes. J Cereb Blood Flow Metab 25:939–948

    PubMed  CAS  Google Scholar 

  192. Lofstedt T, Jogi A, Sigvardsson M, Gradin K, Poellinger L, Pahlman S, Axelson H (2004) Induction of ID2 expression by hypoxia-inducible factor-1: a role in dedifferentiation of hypoxic neuroblastoma cells. J Biol Chem 279: 39223–39231

    PubMed  Google Scholar 

  193. Synnestvedt K et al (2002) Ecto-5’-nucleotidase (CD73) regulation by hypoxia-inducible factor-1 mediates permeability changes in intestinal epithelia. J Clin Invest 110: 993–1002

    PubMed  CAS  Google Scholar 

  194. Segawa K et al (2006) Visfatin in adipocytes is upregulated by hypoxia through HIF1alpha-dependent mechanism. Biochem Biophys Res Commun 349:875–882

    PubMed  CAS  Google Scholar 

  195. Bae SK et al (2006) Hypoxic induction of human visfatin gene is directly mediated by hypoxia-inducible factor-1. FEBS Lett 580:4105–4113

    PubMed  CAS  Google Scholar 

  196. Arany Z, Huang LE, Eckner R, Bhattacharya S, Jiang C, Goldberg MA, Bunn HF, Livingston DM (1996) An essential role for p300/CBP in the cellular response to hypoxia. Proc Natl Acad Sci U S A 93:12969–12973

    PubMed  CAS  Google Scholar 

  197. Ema M, Hirota K, Mimura J, Abe H, Yodoi J, Sogawa K, Poellinger L, Fujii-Kuriyama Y (1999) Molecular mechanisms of transcription activation by HLF and HIF1alpha in response to hypoxia: their stabilization and redox signal-induced interaction with CBP/p300. Embo J 18:1905–1914

    PubMed  CAS  Google Scholar 

  198. Carrero P, Okamoto K, Coumailleau P, O’Brien S, Tanaka H, Poellinger L (2000) Redox-regulated recruitment of the transcriptional coactivators CREB-binding protein and SRC-1 to hypoxia-inducible factor 1alpha. Mol Cell Bio 20:402–415

    PubMed  CAS  Google Scholar 

  199. Zhang W, Tsuchiya T, Yasukochi Y (1999) Transitional change in interaction between HIF-1 and HNF-4 in response to hypoxia. J Hum Genet 44:293–299

    PubMed  CAS  Google Scholar 

  200. Sanchez-Elsner T, Botella LM, Velasco B, Corbi A, Attisano L, Bernabeu C (2001) Synergistic cooperation between hypoxia and transforming growth factor-beta pathways on human vascular endothelial growth factor gene expression. J Biol Chem 276:38527–38535

    PubMed  CAS  Google Scholar 

  201. Mahon PC, Hirota K, Semenza GL (2001) FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity. Genes Dev 15:2675–2686

    PubMed  CAS  Google Scholar 

  202. Fatyol K, Szalay AA (2001) The p14ARF tumor sup­pressor protein facilitates nucleolar sequestration of hypoxia-inducible factor-1alpha (HIF-1alpha ) and inhibits HIF-1-mediated transcription. J Biol Chem 276: 28421–28429

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Visceral Surgery Research Laboratory, Department of Clinical Research, University of Bern, Murtenstrasse 35, 3010, Bern, Switzerland

    Deborah Stroka & Daniel Candinas

Authors
  1. Deborah Stroka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel Candinas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Deborah Stroka .

Editor information

Editors and Affiliations

  1. Inselspital, Universität Bern, Murtenstr. 35, Bern, 3010, Switzerland

    Jean-Francois Dufour

  2. Klinik für Viszeral- und, Universitätsspital Zürich, Rämistr. 100, Zürich, 8091, Switzerland

    Pierre-Alain Clavien

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Stroka, D., Candinas, D. (2010). Hypoxia-Inducible Factor-1 Signaling System. In: Dufour, JF., Clavien, PA. (eds) Signaling Pathways in Liver Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-00150-5_27

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-00150-5_27

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-00149-9

  • Online ISBN: 978-3-642-00150-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation