Differential Roles of Hypoxia-Inducible Factor 1α (HIF-1α) and HIF-2α in Hypoxic Gene Regulation

Molecular and Cellular Biology

Volumn 23, Issue 24, 2003, Pages 9361-9374

  Hu, Cheng Jun ^a   Wang, Li Yi ^b   Chodosh, Lewis A ^a   Keith, Brian ^a   Simon, M Celeste ^a,b  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AROMATIC HYDROCARBON RECEPTOR; CARRIER PROTEIN; GLYCOLYTIC ENZYME; HYPOXIA INDUCIBLE FACTOR 1ALPHA; HYPOXIA INDUCIBLE FACTOR 2ALPHA; OXYGEN; PROTEIN SUBUNIT; TETRACYCLINE; TRANSCRIPTION FACTOR;

ANIMAL CELL; ARTICLE; CELL SPECIFICITY; CELL STRAIN; CELL TYPE; CONTROLLED STUDY; DIMERIZATION; DNA BINDING; DNA MICROARRAY; EMBRYO; EMBRYO CELL; EMBRYO DEVELOPMENT; ENDOTHELIUM CELL; FIBROBLAST; GENE CONTROL; GENE EXPRESSION; GENE FUNCTION; GENE IDENTIFICATION; GENE INDUCTION; GENE TARGETING; GENETIC ENGINEERING; GENETIC TRANSFECTION; HUMAN; HUMAN CELL; HYPOXIA; MOUSE; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN STABILITY; PROTEIN STRUCTURE; SEQUENCE HOMOLOGY; STEM CELL; STRUCTURE ANALYSIS; TRANSACTIVATION; TRANSCRIPTION REGULATION;

ANIMALS; BASE SEQUENCE; BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS; CELL HYPOXIA; CELL LINE; DNA, COMPLEMENTARY; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GLYCOLYSIS; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; MICE; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; RNA, MESSENGER; TRANS-ACTIVATORS; TRANSCRIPTION FACTORS; TRANSFECTION;

ANIMALIA;

EID: 0345491599     PISSN: 02707306     EISSN: None     Source Type: Journal    
DOI: 10.1128/MCB.23.24.9361-9374.2003     Document Type: Article

References (112)

1. Alvarez-Tejado, M., S. Naranjo-Suarez, C. Jimenez, A. C. Carrera, M. O. Landazuri, and L. del Peso. 2001. Hypoxia induces the activation of the phosphatidylinositol 3-kinase/Akt cell survival pathway in PC12 cells: protective role in apoptosis. J. Biol. Chem. 276:22368-22374.
2. Arany, Z., L. E. Huang, R. Eckner, S. Bhattacharya, C. Jiang, M. A. Goldberg, H. F. Bunn, and D. M. Livingston. 1996. An essential role for p300/ CBP in the cellular response to hypoxia. Proc. Natl. Acad. Sci. USA 93:12969-12973.
3. Arsham, A. M., D. R. Plas, C. B. Thompson, and M. C. Simon. 2002. Phosphatidylinositol 3-kinase/Akt signaling is neither required for hypoxic stabilization of HIF-1 alpha nor sufficient for HIF-1-dependent target gene transcription. J. Biol. Chem. 277:15162-15170.
4. Ausserer, W. A., B. Bourrat-Floeck, C. J. Green, K. R. Laderoute, and R. M. Sutherland. 1994. Regulation of c-jun expression during hypoxic and low-glucose stress. Mol. Cell. Biol. 14:5032-5042.
5. Bandyopadhyay, R. S., M. Phelan, and D. V. Faller. 1995. Hypoxia induces AP-1-regulated genes and AP-1 transcription factor binding in human endothelial and other cell types. Biochim. Biophys. Acta 1264:72-78.
6. Binder, C., L. Binder, M. Kroemker, M. Schulz, and W. Hiddemann. 1997. Influence of cycloheximide-mediated downregulation of glucose transport on TNF alpha-induced apoptosis. Exp. Cell Res. 236:223-230.
7. Bonicalzi, M. E., I. Groulx, N. de Paulsen, and S. Lee. 2001. Role of exon 2-encoded beta-domain of the von Hippel-Lindau tumor suppressor protein. J. Biol. Chem. 276:1407-1416.
8. Brar, B. K., A. Stephanou, R. Knight, and D. S. Latchman. 2002. Activation of protein kinase B/Akt by urocortin is essential for its ability to protect cardiac cells against hypoxia/reoxygenation-induced cell death. J. Mol. Cell. Cardiol. 34:483-492.
9. Bruick, R. K. 2000. Expression of the gene encoding the proapoptotic Nip3 protein is induced by hypoxia. Proc. Natl. Acad. Sci. USA 97:9082-9087.
10. Bruick, R. K., and S. L. McKnight. 2001. A conserved family of prolyl-4-hydroxylases that modify HIF. Science 294:1337-1340.
11. Brusselmans, K., F. Bono, P. Maxwell, Y. Dor, M. Dewerchin, D. Collen, J. M. Herbert, and P. Carmeliet. 2001. Hypoxia-inducible factor-2alpha (HIF-2alpha) is involved in the apoptotic response to hypoglycemia but not to hypoxia. J. Biol. Chem. 276:39192-39196.
12. Carmeliet, P., Y. Dor, J. M. Herbert, D. Fukumura, K. Brusselmans, M. Dewerchin, M. Neeman, F. Bono, R. Abramovitch, P. Maxwell, C. J. Koch, P. Ratcliffe, L. Moons, R. K. Jain, D. Collen, E. Keshert, and E. Keshet. 1998. Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature 394:485-490.
13. Carrero, P., K. Okamoto, P. Coumailleau, S. O'Brien, H. Tanaka, and L. Poellinger. 2000. Redox-regulated recruitment of the transcriptional coactivators CREB-binding protein and SRC-1 to hypoxia-inducible factor 1α. Mol. Cell. Biol. 20:402-415.
14. Chandel, N. S., E. Maltepe, E. Goldwasser, C. E. Mathieu, M. C. Simon, and P. T. Schumacker. 1998. Mitochondrial reactive oxygen species trigger hypoxia-induced transcription. Proc. Natl. Acad. Sci. USA 95:11715-11720.
15. 2 sensing. J. Biol. Chem. 275:25130-25138.
16. Chen, E. Y., N. M. Mazure, J. A. Cooper, and A. J. Giaccia. 2001. Hypoxia activates a platelet-derived growth factor receptor/ phosphatidylinositol 3-kinase/Akt pathway that results in glycogen synthase kinase-3 inactivation. Cancer Res. 61:2429-2433.
17. Chi, M. M., J. Pingsterhaus, M. Carayannopoulos, and K. H. Moley. 2000. Decreased glucose transporter expression triggers BAX-dependent apoptosis in the murine blastocyst. J. Biol. Chem. 275:40252-40257.
18. Cockman, M. E., N. Masson, D. R. Mole, P. Jaakkola, G. W. Chang, S. C. Clifford, E. R. Maher, C. W. Pugh, P. J. Ratcliffe, and P. H. Maxwell. 2000. Hypoxia inducible factor-alpha binding and ubiquitylation by the von Hippel-Lindau tumor suppressor protein. J. Biol. Chem. 275:25733-25741.
19. Compernolle, V., K. Brusselmans, T. Acker, P. Hoet, M. Tjwa, H. Beck, S. Plaisance, Y. Dor, E. Keshet, F. Lupu, B. Nemery, M. Dewerchin, P. Van Veldhoven, K. Plate, L. Moons, D. Collen, and P. Carmeliet. 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.
20. Cramer, T., Y. Yamanishi, B. E. Clausen, I. Forster, R. Pawlinski, N. Mackman, V. H. Haase, R. Jaenisch, M. Corr, V. Nizet, G. S. Firestein, H. P. Gerber, N. Ferrara, and R. S. Johnson. 2003. HIF-1alpha is essential for myeloid cell-mediated inflammation. Cell 112:645-657.
21. Denko, N., K. Wernke-Dollries, A. B. Johnson, E. Hammond, C. M. Chiang, and M. C. Barton. 2003. Hypoxia actively represses transcription by inducing negative cofactor 2 (Dr1/DrAP1) and blocking preinitiation complex assembly. J. Biol. Chem. 278:5744-5749.
22. Ebert, B. L., and H. F. Bunn. 1998. Regulation of transcription by hypoxia requires a multiprotein complex that includes hypoxia-inducible factor 1, an adjacent transcription factor, and p300/CREB binding protein. Mol. Cell. Biol. 18:4089-4096.
23. Elvert, G., A. Kappel, R. Heidenreich, U. Englmeier, S. Lanz, T. Acker, M. Rauter, K. Plate, M. Sieweke, G. Breier, and I. Flamme. 2003. 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. 278:7520-7530.
24. Elvert, G., S. Lanz, A. Kappel, and I. Flamme. 1999. mRNA cloning and expression studies of the quail homologue of HIF-2alpha. Mech. Dev. 87:193-197.
25. Ema, M., K. Hirota, J. Mimura, H. Abe, J. Yodoi, K. Sogawa, L. Poellinger, and Y. Fujii-Kuriyama. 1999. Molecular mechanisms of transcription activation by HLF and HIF 1alpha in response to hypoxia: their stabilization and redox signal-induced interaction with CBP/p300. EMBO J. 18:1905-1914.
26. Ema, M., S. Taya, N. Yokotani, K. Sogawa, Y. Matsuda, and Y. Fujii-Kuriyama. 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. USA 94:4273-4278.
27. Epstein, A. C., J. M. Gleadle, L. A. McNeill, K. S. Hewitson, J. O'Rourke, D. R. Mole, M. Mukherji, E. Metzen, M. I. Wilson, A. Dhanda, Y. M. Tian, N. Masson, D. L. Hamilton, P. Jaakkola, R. Barstead, J. Hodgkin, P. H. Maxwell, C. W. Pugh, C. J. Schofield, and P. J. Ratcliffe. 2001. C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell 107:43-54.
28. Favier, J., H. Kempf, P. Corvol, and J. M. Gasc. 1999. Cloning and expression pattern of EPAS1 in the chicken embryo: colocalization with tyrosine hydroxylase. FEBS Lett. 462:19-24.
29. Figueroa, Y. G., A. K. Chan, R. Ibrahim, Y. Tang, M. E. Burow, J. Alam, A. B. Scandurro, and B. S. Beckman. 2002. NF-kappaB plays a key role in hypoxia-inducible factor-1-regulated erythropoietin gene expression. Exp. Hematol. 30:1419-1427.
30. Flamme, I., T. Frohlich, M. von Reutern, A. Kappel, A. Damert, and W. Risau. 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.
31. Gottlob, K., N. Majewski, S. Kennedy, E. Kandel, R. B. Robey, and N. Hay. 2001. Inhibition of early apoptotic events by Akt/PKB is dependent on the first committed step of glycolysis and mitochondrial hexokinase. Genes Dev. 15:1406-1418.
32. Gu, Y. Z., S. M. Moran, J. B. Hogenesch, L. Wartman, and C. A. Bradfield. 1998. Molecular characterization and chromosomal localization of a third alpha-class hypoxia inducible factor subunit, HIF3alpha. Gene Expr. 7:205-213.
33. Hewitson, K. S., L. A. McNeill, M. V. Riordan, Y. M. Tian, A. N. Bullock, R. W. Welford, J. M. Elkins, N. J. Oldham, S. Bhattacharya, J. M. Gleadle, P. J. Ratcliffe, C. W. Pugh, and C. J. Schofield. 2002. Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural family. J. Biol. Chem. 277:26351-26355.
34. Hochachka, P. W., L. T. Buck, C. J. Doll, and S. C. Land. 1996. Uniting theory of hypoxia tolerance: molecular/metabolic defense and rescue mechanisms for surviving oxygen lack. Proc. Natl. Acad. Sci. USA 93:9493-9498.
35. Hogenesch, J. B., W. K. Chan, V. H. Jackiw, R. C. Brown, Y. Z. Gu, M. Pray-Grant, G. H. Perdew, and C. A. Bradfield. 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.
36. Hu, C. J., S. Rao, D. L. Ramirez-Bergeron, L. A. Garrett-Sinha, S. Gerondakis, M. R. Clark, and M. C. Simon. 2001. PU.1/Spi-B regulation of c-rel is essential for mature B cell survival. Immunity 15:545-555.
37. Huang, L. E., Z. Arany, D. M. Livingston, and H. F. Bunn. 1996. Activation of hypoxia-inducible transcription factor depends primarily upon redox-sensitive stabilization of its alpha subunit. J. Biol. Chem. 271:32253-32259.
38. Iliopoulos, O., A. Kibel, S. Gray, and W. G. Kaelin, Jr. 1995. Tumour suppression by the human von Hippel-Lindau gene product. Nat. Med. 1:822-826.
39. Iliopoulos, O., A. P. Levy, C. Jiang, W. G. Kaelin, Jr., and M. A. Goldberg. 1996. Negative regulation of hypoxia-inducible genes by the von Hippel-Lindau protein. Proc. Natl. Acad. Sci. USA 93:10595-10599.
40. Imamura, M., T. Inoguchi, S. Ikuyama, S. Taniguchi, K. Kobayashi, N. Nakashima, and H. Nawata. 2002. ADRP stimulates lipid accumulation and lipid droplet formation in murine fibroblasts. Am. J. Physiol. Endocrinol. Metab. 283:E775-E783.
41. 2 sensing. Science 292:464-468.
42. 2 homeostasis by hypoxia-inducible factor 1 alpha. Genes Dev. 12:149-162.
43. 2-regulated prolyl hydroxylation. Science 292:468-472.
44. Jain, S., E. Maltepe, M. M. Lu, C. Simon, and C. A. Bradfield. 1998. Expression of ARNT, ARNT2, HIF1 alpha, HIF2 alpha and Ah receptor mRNAs in the developing mouse. Mech. Dev. 73:117-123.
45. Jiang, B. H., E. Rue, G. L. Wang, R. Roe, and G. L. Semenza. 1996. Dimerization, DNA binding, and transactivation properties of hypoxia-inducible factor 1. J. Biol. Chem. 271:17771-17778.
46. Jiang, B. H., J. Z. Zheng, S. W. Leung, R. Roe, and G. L. Semenza. 1997. Transactivation and inhibitory domains of hypoxia-inducible factor 1alpha. Modulation of transcriptional activity by oxygen tension. J. Biol. Chem. 272:19253-19260.
47. Jiang, H., R. Guo, and J. A. Powell-Coffman. 2001. The Caenorhabditis elegans hif-1 gene encodes a bHLH-PAS protein that is required for adaptation to hypoxia. Proc. Natl. Acad. Sci. USA 98:7916-7921.
48. Jiang, Z., Y. Zhang, X. Chen, P. Y. Lam, H. Yang, Q. Xu, and A. C. Yu. 2002. Activation of Erk1/2 and Akt in astrocytes under ischemia. Biochem. Biophys. Res. Commun. 294:726-733.
49. Kaelin, W. G., Jr. 2002. Molecular basis of the VHL hereditary cancer syndrome. Nat. Rev. Cancer 2:673-682.
50. Kamura, T., S. Sato, K. Iwai, M. Czyzyk-Krzeska, R. C. Conaway, and J. W. Conaway. 2000. Activation of HIF1alpha ubiquitination by a reconstituted von Hippel-Lindau (VHL) tumor suppressor complex. Proc. Natl. Acad. Sci. USA 97:10430-10435.
51. Kan, O., S. A. Baldwin, and A. D. Whetton. 1994. Apoptosis is regulated by the rate of glucose transport in an interleukin 3 dependent cell line. J. Exp. Med. 180:917-923.
52. Keith, B., D. M. Adelman, and M. C. Simon. 2001. Targeted mutation of the murine arylhydrocarbon receptor nuclear translocator 2 (Arnt2) gene reveals partial redundancy with Arnt. Proc. Natl. Acad. Sci. USA 98:6692-6697.
53. Kondo, K., J. Klco, E. Nakamura, M. Lechpammer, and W. G. Kaelin, Jr. 2002. Inhibition of HIF is necessary for tumor suppression by the von Hippel-Lindau protein. Cancer Cell 1:237-246.
54. Kotch, L. E., N. V. Iyer, E. Laughner, and G. L. Semenza. 1999. Defective vascularization of HIF-1alpha-null embryos is not associated with VEGF deficiency but with mesenchymal cell death. Dev. Biol. 209:254-267.
55. Krieg, M., R. Haas, H. Brauch, T. Acker, I. Flamme, and K. H. Plate. 2000. Up-regulation of hypoxia-inducible factors HIF-1alpha and HIF-2alpha under normoxic conditions in renal carcinoma cells by von Hippel-Lindau tumor suppressor gene loss of function. Oncogene 19:5435-5443.
56. Lando, D., D. J. Peet, J. J. Gorman, D. A. Whelan, M. L. Whitelaw, and R. K. Bruick. 2002. FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. Genes Dev. 16:1466-1471.
57. Lando, D., D. J. Peet, D. A. Whelan, J. J. Gorman, and M. L. Whitelaw. 2002. Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch. Science 295:858-861.
58. Leek, R. D., K. L. Talks, F. Pezzella, H. Turley, L. Campo, N. S. Brown, R. Bicknell, M. Taylor, K. C. Gatter, and A. L. Harris. 2002. 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. 62:1326-1329.
59. Levy, N. S., S. Chung, H. Furneaux, and A. P. Levy. 1998. Hypoxic stabilization of vascular endothelial growth factor mRNA by the RNA-binding protein HuR. J. Biol. Chem. 273:6417-6423.
60. Lin, Z., J. M. Weinberg, R. Malhotra, S. E. Merritt, L. B. Holzman, and F. C. Brosius III. 2000. GLUT-1 reduces hypoxia-induced apoptosis and JNK pathway activation. Am. J. Physiol. Endocrinol. Metab. 278:E958-E966.
61. Liu, L. X., H. Lu, Y. Luo, T. Date, A. J. Belanger, K. A. Vincent, G. Y. Akita, M. Goldberg, S. H. Cheng, R. J. Gregory, and C. Jiang. 2002. Stabilization of vascular endothelial growth factor mRNA by hypoxia-inducible factor 1. Biochem. Biophys. Res. Commun. 291:908-914.
62. Mahon, P. C., K. Hirota, and G. L. Semenza. 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.
63. Maltepe, E., J. V. Schmidt, D. Baunoch, C. A. Bradfield, and M. C. Simon. 1997. Abnormal angiogenesis and responses to glucose and oxygen deprivation in mice lacking the protein ARNT. Nature 386:403-407.
64. Maranchie, J. K., J. R. Vasselli, J. Riss, J. S. Bonifacino, W. M. Linehan, and R. D. Klausner. 2002. The contribution of VHL substrate binding and HIF1-alpha to the phenotype of VHL loss in renal cell carcinoma. Cancer Cell 1:247-255.
65. Masson, N., C. Willam, P. H. Maxwell, C. W. Pugh, and P. J. Ratcliffe. 2001. Independent function of two destruction domains in hypoxia-inducible factor-alpha chains activated by prolyl hydroxylation. EMBO J. 20:5197-5206.
66. Maxwell, P. H., M. S. Wiesener, G. W. Chang, S. C. Clifford, E. C. Vaux, M. E. Cockman, C. C. Wykoff, C. W. Pugh, E. R. Maher, and P. J. Ratcliffe. 1999. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 399:271-275.
67. McNeill, L. A., K. S. Hewitson, T. D. Claridge, J. F. Seibel, L. E. Horsfall, and C. J. Schofield. 2002. Hypoxia-inducible factor asparaginyl hydroxylase (FIH-1) catalyses hydroxylation at the beta-carbon of asparagine-803. Biochem. J. 367:571-575.
68. Moley, K. H., and M. M. Mueckler. 2000. Glucose transport and apoptosis. Apoptosis 5:99-105.
69. O'Donovan, N., M. Galvin, and J. G. Morgan. 1999. Physical mapping of the CXC chemokine locus on human chromosome 4. Cytogenet. Cell Genet. 84:39-42.
70. Ohh, M., C. W. Park, M. Ivan, M. A. Hoffman, T. Y. Kim, L. E. Huang, N. Pavletich, V. Chau, and W. G. Kaelin. 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.
71. Ohtsubo, T., H. J. Park, J. C. Lyons, T. Ohnishi, and C. W. Song. 2000. Effect of acidic environment and p53 on apoptosis induction by hyperthermia. Int. J. Hyperthermia 16:481-491.
72. Onita, T., P. G. Ji, J. W. Xuan, H. Sakai, H. Kanetake, P. H. Maxwell, G. H. Fong, M. Y. Gabril, M. Moussa, and J. L. Chin. 2002. Hypoxia-induced, perinecrotic expression of endothelial Per-ARNT-Sim domain protein-1/hypoxia-inducible factor-2alpha correlates with tumor progression, vascularization, and focal macrophage infiltration in bladder cancer. Clin. Cancer Res. 8:471-480.
73. O'Rourke, J. F., Y. M. Tian, P. J. Ratcliffe, and C. W. Pugh. 1999. Oxygen-regulated and transactivating domains in endothelial PAS protein 1: comparison with hypoxia-inducible factor-1alpha. J. Biol. Chem. 274:2060-2071.
74. Park, H. J., J. C. Lyons, T. Ohtsubo, and C. W. Song. 2000. Cell cycle progression and apoptosis after irradiation in an acidic environment. Cell Death Differ. 7:729-738.
75. Park, S. K., A. M. Dadak, V. H. Haase, L. Fontana, A. J. Giaccia, and R. S. Johnson. 2003. Hypoxia-induced gene expression occurs solely through the action of hypoxia-inducible factor 1alpha (HIF-1alpha): role of cytoplasmic trapping of HIF-2alpha. Mol. Cell. Biol. 23:4959-4971.
76. Pastorino, J. G., N. Shulga, and J. B. Hoek. 2002. Mitochondrial binding of hexokinase II inhibits Bax-induced cytochrome c release and apoptosis. J. Biol. Chem. 277:7610-7618.
77. Paul, R. J., J. Gohla, R. Foll, and H. Schneckenburger. 2000. Metabolic adaptations to environmental changes in Caenorhabditis elegans. Comp. Biochem. Physiol. B Biochem. Mol. Biol. 127:469-479.
78. Peng, J., L. Zhang, L. Drysdale, and G. H. Fong. 2000. The transcription factor EPAS-1/hypoxia-inducible factor 2alpha plays an important role in vascular remodeling. Proc. Natl. Acad. Sci. USA 97:8386-8391.
79. Price, B. D., and S. K. Calderwood. 1992. Gadd45 and Gadd153 messenger RNA levels are increased during hypoxia and after exposure of cells to agents which elevate the levels of the glucose-regulated proteins. Cancer Res. 52:3814-3817.
80. Pugh, C. W., J. F. O'Rourke, M. Nagao, J. M. Gleadle, and P. J. Ratcliffe. 1997. Activation of hypoxia-inducible factor-1: definition of regulatory domains within the alpha subunit. J. Biol. Chem. 272:11205-11214.
81. Robinson, S., and L. A. Franic. 2001. Chemokine GRO1 and the spatial and temporal regulation of oligodendrocyte precursor proliferation. Dev. Neurosci. 23:338-345.
82. Rosenberger, C., S. Mandriota, J. S. Jurgensen, M. S. Wiesener, J. H. Horstrup, U. Frei, P. J. Ratcliffe, P. H. Maxwell, S. Bachmann, and K. U. Eckardt. 2002. Expression of hypoxia-inducible factor-1alpha and -2alpha in hypoxic and ischemic rat kidneys. J. Am. Soc. Nephrol. 13:1721-1732.
83. Ryan, H. E., J. Lo, and R. S. Johnson. 1998. HIF-1 alpha is required for solid tumor formation and embryonic vascularization. EMBO J. 17:3005-3015.
84. Salceda, S., and J. Caro. 1997. Hypoxia-inducible factor 1alpha (HIF-1alpha) protein is rapidly degraded by the ubiquitin-proteasome system under normoxic conditions. Its stabilization by hypoxia depends on redox-induced changes. J. Biol. Chem. 272:22642-22647.
85. Sang, N., J. Fang, V. Srinivas, I. Leshchinsky, and J. Caro. 2002. Carboxyl-terminal transactivation activity of hypoxia-inducible factor 1 alpha is governed by a von Hippel-Lindau protein-independent, hydroxylation-regulated association with p300/CBP. Mol. Cell. Biol. 22:2984-2992.
86. Schipani, E., H. E. Ryan, S. Didrickson, T. Kobayashi, M. Knight, and R. S. Johnson. 2001. Hypoxia in cartilage: HIF-1alpha is essential for chondrocyte growth arrest and survival. Genes Dev. 15:2865-2876.
87. Schmaltz, C., P. H. Hardenbergh, A. Wells, and D. E. Fisher. 1998. Regulation of proliferation-survival decisions during tumor cell hypoxia. Mol. Cell. Biol. 18:2845-2854.
88. Schoemaker, M. H., J. E. Ros, M. Homan, C. Trautwein, P. Liston, K. Poelstra, H. van Goor, P. L. Jansen, and H. Moshage. 2002. Cytokine regulation of pro- and anti-apoptotic genes in rat hepatocytes: NF-kappaB-regulated inhibitor of apoptosis protein 2 (cIAP2) prevents apoptosis. J. Hepatol. 36:742-750.
89. Schroedl, C., D. S. McClintock, G. R. Budinger, and N. S. Chandel. 2002. Hypoxic but not anoxic stabilization of HIF-1alpha requires mitochondrial reactive oxygen species. Am. J. Physiol. Lung Cell. Mol. Physiol. 283:922-931.
90. Schultz, C. J., E. Torres, C. Londos, and J. S. Torday. 2002. Role of adipocyte differentiation-related protein in surfactant phospholipid synthesis by type II cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 283:288-296.
91. Seagroves, T. N., H. E. Ryan, H. Lu, B. G. Wouters, M. Knapp, P. Thibault, K. Laderoute, and R. S. Johnson. 2001. Transcription factor HIF-1 is a necessary mediator of the Pasteur effect in mammalian cells. Mol. Cell. Biol. 21:3436-3444.
92. Semenza, G. L. 1998. Hypoxia-inducible factor 1 and the molecular physiology of oxygen homeostasis. J. Lab. Clin. Med. 131:207-214.
93. 2 homeostasis. Curr. Opin. Genet. Dev. 8:588-594.
94. Semenza, G. L., P. H. Roth, H. M. Fang, and G. L. Wang. 1994. Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1. J. Biol. Chem. 269:23757-23763.
95. Shima, D. T., U. Deutsch, and P. A. D'Amore. 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.
96. Sowter, H. M., P. J. Ratcliffe, P. Watson, A. H. Greenberg, and A. L. Harris. 2001. HIF-1-dependent regulation of hypoxic induction of the cell death factors BNIP3 and NIX in human tumors. Cancer Res. 61:6669-6673.
97. Srinivas, V., L. P. Zhang, X. H. Zhu, and J. Caro. 1999. Characterization of an oxygen/redox-dependent degradation domain of hypoxia-inducible factor alpha (HIF-alpha) proteins. Biochem. Biophys. Res. Commun. 260:557-561.
98. Talks, K. L., H. Turley, K. C. Gatter, P. H. Maxwell, C. W. Pugh, P. J. Ratcliffe, and A. L. Harris. 2000. 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. 157:411-421.
99. Tanimoto, K., Y. Makino, T. Pereira, and L. Poellinger. 2000. Mechanism of regulation of the hypoxia-inducible factor-1 alpha by the von Hippel-Lindau tumor suppressor protein. EMBO J. 19:4298-4309.
100. Tian, H., R. E. Hammer, A. M. Matsumoto, D. W. Russell, and S. L. McKnight. 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.
101. Tian, H., S. L. McKnight, and D. W. Russell. 1997. Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells. Genes Dev. 11:72-82.
102. 2 tension. Proc. Natl. Acad. Sci. USA 92:5510-5514.
103. Wang, G. L., and G. L. Semenza. 1993. Characterization of hypoxia-inducible factor 1 and regulation of DNA binding activity by hypoxia. J. Biol. Chem. 268:21513-21518.
104. Wang, G. L., and G. L. Semenza. 1993. General involvement of hypoxia-inducible factor 1 in transcriptional response to hypoxia. Proc. Natl. Acad. Sci. USA 90:4304-4308.
105. Wang, G. L., and G. L. Semenza. 1995. Purification and characterization of hypoxia-inducible factor 1. J. Biol. Chem. 270:1230-1237.
106. 2-regulated gene expression. FASEB J. 16:1151-1162.
107. Wiesener, M. S., J. S. Jurgensen, C. Rosenberger, C. K. Scholze, J. H. Horstrup, C. Warnecke, S. Mandriota, I. Bechmann, U. A. Frei, C. W. Pugh, P. J. Ratcliffe, S. Bachmann, P. H. Maxwell, and K. U. Eckardt. 2003. Widespread hypoxia-inducible expression of HIF-2alpha in distinct cell populations of different organs. FASEB J. 17:271-273.
108. Wiesener, M. S., H. Turley, W. E. Allen, C. Willam, K. U. Eckardt, K. L. Talks, S. M. Wood, K. C. Gatter, A. L. Harris, C. W. Pugh, P. J. Ratcliffe, and P. H. Maxwell. 1998. Induction of endothelial Proc. Natl. Acad. Sci. domain protein-1 by hypoxia: characterization and comparison with hypoxia-inducible factor-1alpha. Blood 92:2260-2268.
109. Williams, A. C., T. J. Collard, and C. Paraskeva. 1999. An acidic environment leads to p53 dependent induction of apoptosis in human adenoma and carcinoma cell lines: implications for clonal selection during colorectal carcinogenesis. Oncogene 18:3199-3204.
110. Wood, S. M., J. M. Gleadle, C. W. Pugh, O. Hankinson, and P. J. Ratcliffe. 1996. The role of the aryl hydrocarbon receptor nuclear translocator (ARNT) in hypoxic induction of gene expression: studies in ARNT-deficient cells. J. Biol. Chem. 271:15117-15123.
111. Yu, F., S. B. White, Q. Zhao, and F. S. Lee. 2001. Dynamic, site-specific interaction of hypoxia-inducible factor-1alpha with the von Hippel-Lindau tumor suppressor protein. Cancer Res. 61:4136-4142.
112. Yu, F., S. B. White, Q. Zhao, and F. S. Lee. 2001. HIF-1alpha binding to VHL is regulated by stimulus-sensitive proline hydroxylation. Proc. Natl. Acad. Sci. USA 98:9630-9635.