Biology of hypoxia-inducible factor-2α in development and disease

Cell Death and Differentiation

Volumn 15, Issue 4, 2008, Pages 628-634

  Patel, S A ^a   Simon, M C ^a,b  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b HOWARD HUGHES MEDICAL INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADRENOMEDULLIN; CHEMOKINE RECEPTOR CXCR4; CYCLIN D1; CYCLIN D2; EPIDERMAL GROWTH FACTOR RECEPTOR; HYPOXIA INDUCIBLE FACTOR 1ALPHA; HYPOXIA INDUCIBLE FACTOR 2ALPHA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; MYC PROTEIN; NOTCH RECEPTOR; PROTEIN LYSINE 6 OXIDASE; TRANSCRIPTION FACTOR E2F1; TRANSCRIPTION FACTOR TWIST; TRANSFORMING GROWTH FACTOR ALPHA; TUBERIN; VASCULOTROPIN; VON HIPPEL LINDAU PROTEIN;

ANGIOGENESIS; CARCINOGENESIS; CELL PROLIFERATION; ERYTHROPOIESIS; GLIOMA; HEMANGIOBLASTOMA; HUMAN; IRON RESPONSIVE ELEMENT; KIDNEY CARCINOMA; MALIGNANT NEOPLASTIC DISEASE; METASTASIS; NEUROBLASTOMA; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN TARGETING; REVIEW; TISSUE DISTRIBUTION; TISSUE OXYGENATION; TUMOR GROWTH; VASCULAR DISEASE; VON HIPPEL LINDAU DISEASE;

ANIMALS; ANOXIA; BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS; CELL HYPOXIA; CELL TRANSFORMATION, NEOPLASTIC; GENE EXPRESSION REGULATION, NEOPLASTIC; GENOTYPE; HUMANS; MICE; MICE, KNOCKOUT; NEOPLASMS; PHENOTYPE; SIGNAL TRANSDUCTION; TISSUE DISTRIBUTION; TRANSCRIPTION, GENETIC;

EID: 40949088476     PISSN: 13509047     EISSN: 14765403     Source Type: Journal    
DOI: 10.1038/cdd.2008.17     Document Type: Review

References (84)

1. Harris AL. Hypoxia - a key regulatory factor in tumour growth. Nat Rev Cancer 2002; 2: 38-47.
2. Covello KL, Simon MC. HIFs, hypoxia, and vascular development. Curr Top Dev Biol 2004; 62: 37-54.
3. Jain RK. Normalization of tumor vasculature: An emerging concept in antiangiogenic therapy. Science 2005; 307: 58-62.
4. Gu YZ, Hoganesch JB, Bradfield CA. The PAS superfamily: Sensors of environmental and developmental signals. Annu Rev Pharmacol Toxicol 2000; 40: 519-561.
5. 2-regulated prolyl hydroxylation. Science 2001; 292: 468-472.
6. Epstein AC, Gleadle JM, McNeill LA, Hewitson KS, O'Rourke J, Mole DR et al. C. elegans EGL-9 and mammalian homologs define a family dioxygeneses that regulate HIF by prolyl hydroxylation. Cell 2001; 107: 43-54.
7. Maxwell PH, Wiesener MS, Chang GW, Clifford SC, Vaux EC, Cockman ME et al. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 1999; 399: 271-275.
8. Yu F, White SB, Zhao Q, Lee FS, HIF-1alpha binding to VHL is regulated by stimulus-sensitive proline hydroxylation. Proc Natl Acad Sci USA 2000; 98: 9630-9635.
9. Bruick RK, McKnight SL. A conserved family of prolyl-4-hydroxylases that modify HIF. Science 2001; 294: 1337-1340.
10. Wenger RH, Stiehl DP, Camenisch G. Integration of oxygen signaling at the consensus HRE. Sci STKE 2005; 2005: Re12.
11. Tian H, Mcknight SL, Russell DW. Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells. Genes Dev 1997; 11: 72-82.
12. Ema M, Taya S, Yokotani N, Sogawa K, Matsuda Y, Fuji-Kuriyama Y. A novel bHLH-PAS factor with close sequence similarity to hypoxa-inducible factor 1alpha regulates the VEGIF expression and is potentially involved in lung and vascular development. Proc Natl Acad Sci USA 1997; 94: 4273-4278.
13. Flamme I, Frohlich T, von Reutern M, Kappel A, Damert A, Risau W. 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 1997; 63: 51-60.
14. Hogenesch JB, Chan WK, Jackiw VH, Brown RC, Gu Y7, Pray-Grant M et al Characterization of a subset of the basic-helix-loop-helix-PAS superfamily that interacts with components of the dioxin signaling pathway. J Biol Chem 1997; 272: 8581-8593.
15. Tian H, Hammer RE, Matsumoto AM, Russell DW, McKnight SL. The hypoxia-responsive transcription factor EPAS1 is essential for catecholamine homeostasis and protection against heart failure during embryonic development. Genes Dev 1998; 12: 3320-3324.
16. Wiesener MS, Jurgensen JS, Rosenberger C, Scholze CK, Horstrup JH, Warnecke C et al. Widespread hypoxia-inducible expression of HIF-2alpha in distinct cell populations of different organs. FASEB J 2003; 17: 271-273.
17. Holmquist-Mengelbier L, Fredlund E, Lofstedt T, Noguera R, Navarro S, Nilsson H et al. Recruitment of HIF-1alpha and HIF-2alpha to common target genes is differentially regulated in neuroblastoma: HIF-2alpha promotes an aggressive phenotype. Cancer Cell 2006; 10: 413-423.
18. Wiesener MS, Turley H, Allen WE, Willam C, Eckardt KU, Talks KL et al Induction of endothelial PAS domain protein-1 by hypoxia: characterization and comparison with hypoxia-indudble factor-1alpha. Blood 1998; 92: 2260-2268.
19. Compernolle V, Brusselmans K, Acker T, Host P, Tjwa M, Beck H et al 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 2002; 8: 702-710.
20. Jurgensen JS, Rosenberger C, Wiesener MS, Warnecke C, Horstrup JH, Grafe M et al. Persistent induction of HIF-1alpha and -2alpha in cardiomyocytes and stromal cells of ischemic myocardium. FASEB J 2004; 18: 1415-1417.
21. Hu CJ, Wang LY, Chodosh LA, Keith B, Simon MC. Differential roles of hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha in hypoxic gene regulation. Mol Cell Biol 2003; 23: 9361-9374.
22. Warnecke C, Zaborowska Z, Kurreck J, Erdmann VA, Frei U, Wiesener M et al. Differentiating the functional role of hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha (EPAS-1) by the use of RNA interference: Erythropoietin is a HIF-2alpha target gene in Hep3B and Kelly cells. FASEB J 2004; 18: 1462-1464.
23. Wang V, Davis DA, Haque M, Huang LE, Yarchoan R. Differential gene up-regulation by hypoxia-inducible factor-1alpha and hypoxia-inducible factor-2alpha in HEK293T cells. Cancer Res 2005; 65: 3299-3306.
24. Raval RR, Lau KW, Tran MG, Sowter HM, Mandriota SJ, Li JL et al. Contrasting properties of hypoxia-inducible factor 1 (HIF-1) and HIF-2 in von Hippel-Lindau-associated renal cell carcinoma. Mol Cell Biol 2005; 25: 5675-5686.
25. Hu CJ, Iyer S, Sataur A, Covello KL, Chodosh LA, Simon MC. Differential regulation of the transcriptional activities of hypoxia-inducible factor 1 alpha (HIF-1alpha) and HIF-2alpha in stem cells. Mol Cell Biol 2006; 26: 3514-3526.
26. Grabmaier K, de Weijert MCA, Verhaegh GW, Schalken JA, Oosterwijk E. Strict regulation of CAIX(G250/MN) by HIF-1alpha in clear cell renal cell carcinoma. Oncogene 2004; 23: 5624-5631.
27. Baba M, Hirai S, Yamada-Okabe H, Hamada K, Tabuchi H, Kobayashi K et al. Loss of von Hippel-Lindau protein causes cell density dependent deregulation of CyclinD1 expression through hypoxia-inducible factor. Oncogene 2003; 22: 2728-2738.
28. Gunaratnam L, Morley M, Franovic A, de Paulsen N, Mekhail K, Parolin DA et al. Hypoxia inducible factor activates the transforming growth factor-alpha/epidermal growth factor receptor growth stimulatory pathway in VHL(-/-) renal cell carcinoma cells. J Biol Chem 2003; 278 44966-44974.
29. Covello KL, Kohler J, Yu H, Gordan JD, Arsham AM, Hu CJ et al. HIF-2alpha regulates Oct-4: Effects of hypoxia on stem cell function, embryonic development, and tumor growth. Genes Dev 2006; 20: 557-570.
30. Gort EH, van Haaften G, Verlaan I, Groot AJ, Plasterk RH, Shvarts A et al. The TWIST1 oncogene is a direct target of hypoxia-inducible factor-2alpha. Oncogene 2007 [e-pub ahead of print].
31. Gruber M, Hu CJ, Johnson RS, Brown EJ, Keith B, Simon MC. Acute postnatal ablation of Hif-2alpha results in anemia. Proc Natl Acad Sci USA 2007; 104: 2301-2306.
32. O'Rourke JF, Tian YM, Ratcliffe PJ, Pugh CW. Oxygen-regulated and transactivating domais in endothelial PAS protein 1: Comparison with hypoxia-inducible factor-1alpha. J Biol Chem 1999; 274: 2060-2071.
33. Lando D, Peet DJ, Gorman JJ, Whelan DA, Whitelaw ML, Bruick RK. FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. Genes Dev 2002; 16: 1466-1471.
34. Mahon PC, Hirota K, Semenza GL. FIH-1: A novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity. Genes Dev 2001; 15: 2675-2686.
35. Lau KW, Tian YM, Raval RR, Ratcliffe PJ, Pugh CW. Target gene selectivity hypoxia-inducible factor-alpha in renal cancer cells is conveyed by post-DNA-binding mehanisms. Br J Cancer 2007; 96 1284-1292.
36. Hu CJ, Sataur A, Wang L, Chen H, Simon MC. The N-terminal transactivation domain confers target gene specificity of hypoxia inducible factors HIF-1\{alpha\} and HIF-2. Mol Biol Cell 2007; 18: 4528-4542.
37. Elvert G, Kappel A, Heidenreich R, Englmeier U, Lanz S, Acker T et al Cooperative interaction of hypoxia-inducible factor-2alpha (HIF-2alpha) and Ets-1 in the transcriptional activation of vascular endothelial growth factor receptor-2 (Flk-1). J Biol Chem 2003; 278: 7520-7530.
38. Aprelikova 0, Wood M, Tackett S, Chandramouli GV, Barrett JC. Role of ETS transcription factors in the hypoxia-inducible factor-2 target gene selection. Cancer Res 2006; 66: 5641-5647.
39. Peng J, Zhang L, Drysdale L, Fong GH. The transcription factor EPAS-1/ hypoxia-inducible factor 2alpha plays an important role in vascular remodeling. Proc Natl Acad Sci USA 2000; 97: 8386-8391.
40. -/- mice. Nat Genet 2003; 35: 331-340.
41. 2-responsive sequences on the tyrosine hydroxylase gene. J Biol Chem 1995; 270: 23774-23779.
42. Brusselmans K, Compernolle V, Tjwa M, Wiesener MS, Maxwell PH, Collen D et al. Heterozygous deficiency of hypoxia-inducible factor-2alpha protects mice against pulmonary hypertension and right ventricular dysfunction during prolonged hypoxia. J Clin Invest 2003; 111 1519-1527.
43. Scortegagna M, Morris MA, Oktay Y, Bennett M, Garcia JA. The HIF family member EPAS1/HIF-2alpha is required for normal hematopoiesis in mice. Blood 2003; 102: 1634-1640.
44. Scortegagna M, Ding K, Zhang 0, Oktay Y, Bennett MJ, Bennett M et al HIF-2alpha regulates murine hematopoietic development in an arythropoietin-dependent manner. Blood 2005; 105: 3133-3140.
45. Covello KL, Simon MC, Keith B. Targeted replacement of hypoxia-inducible factor-1alpha by a hypoxia-inducible factor-2alpha knock-in allele promotes tumor growth. Cancer Res 2005; 65: 2277-2286.
46. Rankin EB, Biju MP, Liu Q, Unger TL, Rha J, Johnson RS et al. Hypoxia-inducible factor-2 (HIF-2) regulates hepatic erythropoietin in vivo. J Clin Invest 2007; 117: 1068-1077.
47. Chavez JC, Baranova 0, Lin J, Pichiule P. The transcriptional activator hypoxia inducible factor 2 (HIF-2/EPAS-1) regulates the oxygen-dependent expression of erythropoietin in cortical astrocytes. J Neurosci 2006; 26: 9471-9481.
48. Rolfs A, Kvietikova I, Gassmann M, Wenger RH. Oxygen-regulated transferrin expression is mediated by hypoxia-inducible factor-1. J Biol Chem 1997; 272: 20055-20062.
49. Hentze MW, Muckenthaler MU, Andrews NC. Balancing acts: Molecular control of mammalian iron metabolism. Cell 2004; 117: 285-297.
50. Sanchez M, Galy B, Muckenthaler MU, Hentze MW. Iron-regulatory proteins limit hypoxia-inducible factor-2alpha expression in iron deficiency. Nat Struct Mol Biol 2007; 14: 420-426.
51. Kaelin Jr WG. Molecular basis of the VHL hereditary cancer syndrome. Nat Rev Cancer 2002; 2: 673-682.
52. Kim WY, Kaelin WG. Role of VHL gone mulation in human cancer. J Clin Oncol 2004; 22: 4991-5004.
53. Mandriota SJ, Turner KJ, Davies DR, Murray PG, Morgan NV, Sowter HM et al. HIF activation identidfies early lesions in VHL kidneys: evidence for site-specific tumor suppressor function in the nephron. Cancer Cell 2002; 1: 459-468.
54. Maranchie JK, Vasselli JR, Riss J, Bonifacino JS, Linehan WM, Klausner RD. The contribution of VHL substrate binding and HIF1-alpha to the phenotype of VHL loss in renal cell carcinoma. Cancer Cell 2002; 1: 247-255.
55. Kondo K, Klco J, Nakamura E, Lechpammer M, Kaelin Jr WG. Inhibition of HIF is necessary for tumor suppression by the von Hippel-Lindau protein. Cancer Cell 2002; 1: 237-246.
56. Kondo K, Kim WY, Lechpammer M, Kaelin Jr WG. Inhibition of HIF2alpha is sufficient to suppress pVHL-defective tumor growth. PLoS Biol 2003; 1: E83.
57. Li L, Zhang L, Zhang X, Yen Q, Minamishima YA, Olumi AF et al. Hypoxia-inducible factor linked to differential kidney cancer risk seen with type 2A and type 2B VHL mutations. Mol Cell Biol 2007; 27 5381-5392.
58. Rathmell WK, Hickey MM, Bezman NA, Chmielecki CA, Carraway NC, Simon MC. In vitro and in vivo models analyzing von Hippel-Lindau disease-specific mutations. Cancer Res 2004; 64: 8595-8603.
59. Hickey M, Rathmell WK. Lam JC, Bezman NA, Simon MC. von Hippel-Lindau mutation in mice recapitulates Chuvash polycythemia via hypoxia-inducible factor-2a signaling and splenic erythropoiesis. J Clin Invest 2007; 117: 3879-3889.
60. Liu MY, Poellinger L, Walker CL. Up-regulation of hypoxia-inducible factor 2alpha in renal cell carcinoma associated with loss of Tsc-2 tumor suppressor gene. Cancer Res 2003; 63: 2675-2680.
61. -/- renal cancer. Cancer Res 2005; 65: 5221-5230.
62. de Paulsen N, Brychzy A, Foumier MC, Klausner RD, Gnarra JR, Pause A et al. Role of transforming growth factor-alpha in von Hippel-Lindau (VHL)(-/-) dear cell renal carcinoma cell proliferation: A possible mechanism coupling VHL tumor suppressor inactivation and tumorigenesis. Proc Natl Acad Sci USA 2001; 98: 1387-1392.
63. Yan Q, Bartz S, Mao M. Li L, Kaelin Jr WG. The hypoxia-inducible factor 2alpha N-terminal and C-terminal transactivation domains cooperate to promote renal tumorigenesis in vivo. Mol Cell Biol 2007; 27: 2092-2102.
64. Koshiji M, Kapeyama Y. Pete EA, Horikawa I, Barrett JC, Huang LE. HIF-1alpha induces cell cycle arrest by functionally counteracting Myc. EMBO J 2004; 23: 1949-1956.
65. Gordan JD, Bertout JA, Hu CJ, Diehl JA, Simon MC. HIF-2alpha promotes hypoxic cell proliferation by enhancing c-myc transcriptional activity. Cancer Cell 2007; 11: 335-347.
66. Zhang H, Gao P, Fukuda R, Kumar G, Krishnamachary B, Zeller Kl et al HIF-1 inhibits mitochondrial biogenesis and cellular respiration in VHL-deficient renal cell carcinoma by repression of C-MYC activity. Cancer Cell 2007; 11: 407-420.
67. Com PG, Ricci MS, Scata KA, Arsham AM, Simon MC, Dicker DT et al. Mxi1 is induced by hypoxia in a HIF-1-dependent manner and protects cells from c-Myc-induced apoptosis. Cancer Biol Ther 2005; 4 1285-1294.
68. Gustafsson MV, Zheng X, Pereira T, Gradin K, Jin S, Lundkvist J et al Hypoxia requires notch signaling to maintain the undifferentiated cell state. Dev Cell 2005; 9: 617-628.
69. Condeelis J, Pollard JW. Macrophages: Obligate partners for tumor cell migration, invasion, and metastasis. Cell 2006; 124: 263-266.
70. Talks KL, Turley H, Getter KC, Maxwell PH, Pugh CW, Ratcliffe PJ et al. The expression and distribution of the hypoxia-inducible factors HIF-1alpha and HIF-2alpha in normal human tissues, cancers, and tumor-associated macrophages. Am J Pathol 2000; 157: 411-421.
71. Leek RD, Talks KL, Pezzella F, Turley H, Campo L, Brown NS et al. Relation of hypoxia-inducible factor-2 alpha (HIF-2 alpha) expression in tumor-infiltrative macrophages to tumor angiogenesis and the oxidative thymidine phosphorylase pathway in human breast cancer. Cancer Res 2002; 62: 1326-1329.
72. Staller P, Sulitkova J, Lisztwan J, Moch H, Oakeley EJ, Krek W. Chemokine receptor CXCR4 downregulated by von Hippel-Lindau tumour suppressor pVHL. Nature 2003; 425: 307-311.
73. Erler JT, Bennewith KL, Nicolau M, Dornhofer N, Kong C, Le QT et al Lysyl oxidase is essential for hypoxia-induced metastasis. Nature 2006; 440: 1222-1226.
74. Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C et al Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 2004; 117: 927-939.
75. Jogi A, Ora I, Nilsson H, Lindeheim A, Makino Y, Poellinger L et al Hypoxia alters gene expression in human neuroblastoma cells toward an immature and neural crest-like phenotype. Proc Natl Acad Sci USA 2002; 99: 7021-7026.
76. Acker T, Diez-Juan A, Aragones J, Tjwa. M, Brusselmans K, Moons L et al. Genetic evidence for a tumor suppressor role of HIF-2alpha. Cancer Cell 2005; 8: 131-141.
77. Brusselmans K, Bono F, Maxwell P, Dor Y, Dewerchin M, Cohen D et al Hypoxia-inducible factor-2alpha (HIF-2alpha) is involved in the apoptotic response to hypoglycemia but not to hypoxia. J Biol Chem 2001; 276: 39192-39196.
78. Gordan JD, Thompson CB, Simon MC. HIF and c-Myc: Sibling rivals for control of cancer cell metabolism and proliferation. Cancer Cell 2007; 12: 108-113.
79. Mack FA, Rathmell WK, Arsham AM, Gnarra J, Keith B, Simon MC. Loss of pVHL is sufficient to cause HIF dysregulation in primary cells but does not promote tumor growth. Cancer Cell 2003; 3: 75-88.
80. -/- fibrosarcomas is associated with elevated levels of cyclin kinase inhibitors p21 and p27. Mol Cell Biol 2005; 25: 4565-4578.
81. Rankin EB, Tomaszewski JE, Haase VH. Renal cyst development in mice with conditional inactivation of the von Hippel-Lindau tumor suppressor. Cancer Res 2006; 66: 2576-2583.
82. Melillo G. Targeting hypoxia cell signaling for cancer therapy. Cancer Metastasis Rev 2007; 26: 341-352.
83. Carroll VA, Ashcroft M. Role of hypoxia-inducible factor (HIF)-1alpha versus HIF-2alpha in the regulation of HIF target genes in response to hypoxia, insulin-like growth factor-1, or loss of von Hippel-Lindau function: Implications for targeting the HIF pathway. Cancer Res 2006; 66: 6264-6270.
84. Kung AL, Zabludoff SD, France DS, Freedman SJ, Tanner EA, Vieira A et al. Small molecule blockade of transcriptional coactivation of the hypoxia-inducible factor pathway. Cancer Cell 2004; 6: 33-43.