The updated biology of hypoxia-inducible factor

EMBO Journal

Volumn 31, Issue 11, 2012, Pages 2448-2460

  Greer, Samantha N ^a   Metcalf, Julie L ^a   Wang, Yi ^a   Ohh, Michael ^a  

^a UNIVERSITY OF TORONTO   (Canada)

Author keywords

development; HIF; hypoxia; immunity; stem cell biology

Indexed keywords

HYPOXIA INDUCIBLE FACTOR; VON HIPPEL LINDAU PROTEIN;

CARDIOVASCULAR DISEASE; CELL HYPOXIA; CELL METABOLISM; DEVELOPMENT; HUMAN; IMMUNITY; NEOPLASM; NONHUMAN; OXYGEN SENSING; OXYGEN TENSION; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN FUNCTION; REGULATORY MECHANISM; REVIEW; STEM CELL;

ANIMALS; ANOXIA; BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS; CARRIER PROTEINS; EMBRYONIC DEVELOPMENT; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1; IMMUNITY; MEMBRANE PROTEINS; MICE; OXYGEN; RECEPTORS, NOTCH; SIRTUIN 3; THYROID HORMONES;

EUKARYOTA; MAMMALIA;

EID: 84861845402     PISSN: 02614189     EISSN: 14602075     Source Type: Journal    
DOI: 10.1038/emboj.2012.125     Document Type: Review

References (131)

1. Ahn BH, Kim HS, Song S, Lee IH, Liu J, Vassilopoulos A, Deng CX, Finkel T (2008) A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis. Proc Natl Acad Sci USA 105: 14447-14452
2. 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 USA 93: 12969-12973 (Pubitemid 26382753)
3. Bell EL, Emerling BM, Ricoult SJ, Guarente L (2011) SirT3 suppresses hypoxia inducible factor 1alpha and tumor growth by inhibiting mitochondrial ROS production. Oncogene 30: 2986-2996
4. Bell EL, Guarente L (2011) The SirT3 divining rod points to oxidative stress. Mol Cell 42: 561-568
5. 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 (Pubitemid 29045116)
6. Bidla G, Dushay MS, Theopold U (2007) Crystal cell rupture after injury in Drosophila requires the JNK pathway, small GTPases and the TNF homolog Eiger. J Cell Sci 120: 1209-1215 (Pubitemid 46711839)
7. Brizel DM, Dodge RK, Clough RW, Dewhirst MW (1999) Oxygenation of head and neck cancer: changes during radiotherapy and impact on treatment outcome. Radiother Oncol 53: 113-117
8. Brook FA, Gardner RL (1997) The origin and efficient derivation of embryonic stem cells in the mouse. Proc Natl Acad Sci USA 94: 5709-5712 (Pubitemid 27241834)
9. Brunelle JK, Bell EL, Quesada NM, Vercauteren K, Tiranti V, Zeviani M, Scarpulla RC, Chandel NS (2005) Oxygen sensing requires mitochondrial ROS but not oxidative phosphorylation. Cell Metab 1: 409-414 (Pubitemid 43960624)
10. Bruning U, Cerone L, Neufeld Z, Fitzpatrick SF, Cheong A, Scholz CC, Simpson DA, Leonard MO, Tambuwala MM, Cummins EP, Taylor CT (2011) MicroRNA-155 promotes resolution of hypoxia-inducible factor 1alpha activity during prolonged hypoxia. Mol Cell Biol 31: 4087-4096
11. Camus A, Perea-Gomez A, Moreau A, Collignon J (2006) Absence of Nodal signaling promotes precocious neural differentiation in the mouse embryo. Dev Biol 295: 743-755 (Pubitemid 43927707)
12. 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 (Pubitemid 47592916)
13. Chamboredon S, Ciais D, Desroches-Castan A, Savi P, Bono F, Feige JJ, Cherradi N (2011) Hypoxia-inducible factor-1alpha mRNA: a new target for destabilization by tristetraprolin in endothelial cells. Mol Biol Cell 22: 3366-3378
14. Chen J, Imanaka N, Griffin JD (2010) Hypoxia potentiates Notch signaling in breast cancer leading to decreased E-cadherin expression and increased cell migration and invasion. Br J Cancer 102: 351-360
15. Chen R, Dioum EM, Hogg RT, Gerard RD, Garcia JA (2011) Hypoxia increases sirtuin 1 expression in a hypoxia-inducible factordependent manner. J Biol Chem 286: 13869-13878
16. 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 (Pubitemid 350007694)
17. Christofk HR, Vander Heiden MG, Harris MH, Ramanathan A, Gerszten RE, Wei R, Fleming MD, Schreiber SL, Cantley LC (2008) The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature 452: 230-233 (Pubitemid 351380249)
18. Cimen H, Han MJ, Yang Y, Tong Q, Koc H, Koc EC (2010) Regulation of succinate dehydrogenase activity by SIRT3 in mammalian mitochondria. Biochemistry 49: 304-311
19. Coleman ML, McDonough MA, Hewitson KS, Coles C, Mecinovic J, Edelmann M, Cook KM, Cockman ME, Lancaster DE, Kessler BM, Oldham NJ, Ratcliffe PJ, Schofield CJ (2007) Asparaginyl hydroxylation of the Notch ankyrin repeat domain by factor inhibiting hypoxia-inducible factor. J Biol Chem 282: 24027-24038 (Pubitemid 47328043)
20. 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 (Pubitemid 34651384)
21. Cramer T, Yamanishi Y, Clausen BE, Forster I, Pawlinski R, Mackman N, Haase VH, Jaenisch R, Corr M, Nizet V, Firestein GS, Gerber HP, Ferrara N, Johnson RS (2003) HIF-1alpha is essential for myeloid cell-mediated inflammation. Cell 112: 645-657 (Pubitemid 36331777)
22. Cummins EP, Berra E, Comerford KM, Ginouves A, Fitzgerald KT, Seeballuck F, Godson C, Nielsen JE, Moynagh P, Pouyssegur J, Taylor CT (2006) Prolyl hydroxylase-1 negatively regulates IkappaB kinase-beta, giving insight into hypoxia-induced NFkappaB activity. Proc Natl Acad Sci USA 103: 18154-18159 (Pubitemid 44871628)
23. Cummins EP, Seeballuck F, Keely SJ, Mangan NE, Callanan JJ, Fallon PG, Taylor CT (2008) The hydroxylase inhibitor dimethyloxalylglycine is protective in a murine model of colitis. Gastroenterology 134: 156-165
24. Dang EV, Barbi J, Yang HY, Jinasena D, Yu H, Zheng Y, Bordman Z, Fu J, Kim Y, Yen HR, Luo W, Zeller K, Shimoda L, Topalian SL, Semenza GL, Dang CV, Pardoll DM, Pan F (2011) Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1. Cell 146: 772-784
25. David CJ, Chen M, Assanah M, Canoll P, Manley JL (2010) HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer. Nature 463: 364-368
26. De Strooper B, Annaert W, Cupers P, Saftig P, Craessaerts K, Mumm JS, Schroeter EH, Schrijvers V, Wolfe MS, Ray WJ, Goate A, Kopan R (1999) A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature 398: 518-522
27. Deng S, Yang Y, Han Y, Li X, Wang X, Zhang Z, Wang Y (2012) UCP2 inhibits ROS-mediated apoptosis in A549 under hypoxic conditions. PLoS One 7: e30714
28. Dioum EM, Chen R, Alexander MS, Zhang Q, Hogg RT, Gerard RD, Garcia JA (2009) Regulation of hypoxia-inducible factor 2alpha signaling by the stress-responsive deacetylase sirtuin 1. Science 324: 1289-1293
29. 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 (Pubitemid 29158534)
30. Epstein AC, Gleadle JM, McNeill LA, Hewitson KS, O'Rourke J, Mole DR, Mukherji M, Metzen E, Wilson MI, Dhanda A, Tian YM, Masson N, Hamilton DL, Jaakkola P, Barstead R, Hodgkin J, Maxwell PH, Pugh CW, Schofield CJ, Ratcliffe PJ (2001) C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell 107: 43-54 (Pubitemid 32972036)
31. Evans MJ, Kaufman MH (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292: 154-156 (Pubitemid 11050741)
32. Finley LW, Carracedo A, Lee J, Souza A, Egia A, Zhang J, Teruya-Feldstein J, Moreira PI, Cardoso SM, Clish CB, Pandolfi PP, Haigis MC (2011a) SIRT3 opposes reprogramming of cancer cell metabolism through HIF1α destabilization. Cancer Cell 19: 416-428
33. Finley LW, Haas W, Desquiret-Dumas V, Wallace DC, Procaccio V, Gygi SP, Haigis MC (2011b) Succinate dehydrogenase is a direct target of sirtuin 3 deacetylase activity. PLoS One 6: e23295
34. Fischer B, Bavister BD (1993) Oxygen tension in the oviduct and uterus of rhesus monkeys, hamsters and rabbits. J Reprod Fertil 99: 673-679 (Pubitemid 24052018)
35. Fortini ME (2009) Notch signaling: the core pathway and its posttranslational regulation. Dev Cell 16: 633-647
36. Fox SB, Braganca J, Turley H, Campo L, Han C, Gatter KC, Bhattacharya S, Harris AL (2004) CITED4 inhibits hypoxia-activated transcription in cancer cells, and its cytoplasmic location in breast cancer is associated with elevated expression of tumor cell hypoxia-inducible factor 1alpha. Cancer Res 64: 6075-6081 (Pubitemid 39129407)
37. Frede S, Stockmann C, Freitag P, Fandrey J (2006) Bacterial lipopolysaccharide induces HIF-1 activation in human monocytes via p44/42 MAPK and NF-kappaB. Biochem J 396: 517-527 (Pubitemid 44228166)
38. 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 (Pubitemid 32436196)
39. 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 (Pubitemid 28527216)
40. Gustafsson MV, Zheng X, Pereira T, Gradin K, Jin S, Lundkvist J, Ruas JL, Poellinger L, Lendahl U, Bondesson M (2005) Hypoxia requires notch signaling to maintain the undifferentiated cell state. Dev Cell 9: 617-628 (Pubitemid 41555144)
41. Hara S, Hamada J, Kobayashi C, Kondo Y, Imura N (2001) Expression and characterization of hypoxia-inducible factor (HIF)-3alpha in human kidney: suppression of HIF-mediated gene expression by HIF-3alpha. Biochem Biophys Res Commun 287: 808-813 (Pubitemid 32953545)
42. Harris TJ, Grosso JF, Yen HR, Xin H, Kortylewski M, Albesiano E, Hipkiss EL, Getnet D, Goldberg MV, Maris CH, Housseau F, Yu H, Pardoll DM, Drake CG (2007) Cutting edge: an in vivo requirement for STAT3 signaling in TH17 development and TH17- dependent autoimmunity. J Immunol 179: 4313-4317
43. Hitosugi T, Kang S, Vander HMG, Chung TW, Elf S, Lythgoe K, Dong S, Lonial S, Wang X, Chen GZ, Xie J, Gu TL, Polakiewicz RD, Roesel JL, Boggon TJ, Khuri FR, Gilliland DG, Cantley LC, Kaufman J, Chen J (2009) Tyrosine phosphorylation inhibits PKM2 to promote the Warburg effect and tumor growth. Sci Signal 2: ra73
44. Hoffman DL, Salter JD, Brookes PS (2007) Response of mitochondrial reactive oxygen species generation to steady-state oxygen tension: implications for hypoxic cell signaling. Am J Physiol Heart Circ Physiol 292: H101-H108 (Pubitemid 46105167)
45. Huang C, Han Y, Wang Y, Sun X, Yan S, Yeh ET, Chen Y, Cang H, Li H, Shi G, Cheng J, Tang X, Yi J (2009) SENP3 is responsible for HIF-1 transactivation under mild oxidative stress via p300 de-SUMOylation. EMBO J 28: 2748-2762
46. 2-dependent degradation domain via the ubiquitin-proteasome pathway. Proc Natl Acad Sci USA 95: 7987-7992
47. Imai S, Armstrong CM, Kaeberlein M, Guarente L (2000) Transcriptional silencing and longevity protein Sir2 is an NADdependent histone deacetylase. Nature 403: 795-800 (Pubitemid 30111843)
48. Ivan M, Kondo K, Yang H, Kim W, Valiando J, Ohh M, Salic A, Asara JM, Lane WS, Kaelin Jr WG (2001) HIFalpha targeted for VHLmediated destruction by proline hydroxylation: implications for O2 sensing. Science 292: 464-468 (Pubitemid 32335941)
49. Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, Cua DJ, Littman DR (2006) The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126: 1121-1133 (Pubitemid 44380299)
50. 2-regulated prolyl hydroxylation. Science 292: 468-472
51. James D, Levine AJ, Besser D, Hemmati-Brivanlou A (2005) TGFbeta/activin/nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cells. Development 132: 1273-1282 (Pubitemid 40528787)
52. Jantsch J, Chakravortty D, Turza N, Prechtel AT, Buchholz B, Gerlach RG, Volke M, Glasner J, Warnecke C, Wiesener MS, Eckardt KU, Steinkasserer A, Hensel M, Willam C (2008) Hypoxia and hypoxia-inducible factor-1 alpha modulate lipopolysaccharide- induced dendritic cell activation and function J Immunol 180: 4697-4705
53. Jiang BH, Rue E, Wang GL, Roe R, Semenza GL (1996) Dimerization, DNA binding, and transactivation properties of hypoxia-inducible factor 1. J Biol Chem 271: 17771-17778 (Pubitemid 26250751)
54. Jiang BH, Zheng JZ, Leung SW, Roe R, Semenza GL (1997) Transactivation and inhibitory domains of hypoxia-inducible factor 1alpha. Modulation of transcriptional activity by oxygen tension. J Biol Chem 272: 19253-19260 (Pubitemid 27337716)
55. Jogi A, Ora I, Nilsson H, Lindeheim A, Makino Y, Poellinger L, Axelson H, Pahlman S (2002) Hypoxia alters gene expression in human neuroblastoma cells toward an immature and neural crest-like phenotype. Proc Natl Acad Sci USA 99: 7021-7026 (Pubitemid 34526250)
56. Kaelin Jr.WG, Ratcliffe PJ (2008) Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol Cell 30: 393-402 (Pubitemid 351681994)
57. Karhausen J, Furuta GT, Tomaszewski JE, Johnson RS, Colgan SP, Haase VH (2004) Epithelial hypoxia-inducible factor-1 is protective in murine experimental colitis. J Clin Invest 114: 1098-1106 (Pubitemid 39578699)
58. Khan N, Mupparaju S, Hou H, Williams BB, Swartz H (2012) Repeated assessment of orthotopic glioma pO(2) by multi-site EPR oximetry: a technique with the potential to guide therapeutic optimization by repeated measurements of oxygen. J Neurosci Methods 204: 111-117
59. Kim HS, Patel K, Muldoon-Jacobs K, Bisht KS, Aykin-Burns N, Pennington JD, van der Meer R, Nguyen P, Savage J, Owens KM, Vassilopoulos A, Ozden O, Park SH, Singh KK, Abdulkadir SA, Spitz DR, Deng CX, Gius D (2010) SIRT3 is a mitochondrialocalized tumor suppressor required for maintenance of mitochondrial integrity and metabolism during stress. Cancer Cell 17: 41-52
60. Kim JW, Tchernyshyov I, Semenza GL, Dang CV (2006) HIF-1- mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab 3: 177-185
61. Koivunen P, Hirsila M, Remes AM, Hassinen IE, Kivirikko KI, Myllyharju J (2007) Inhibition of hypoxia-inducible factor (HIF) hydroxylases by citric acid cycle intermediates: possible links between cell metabolism and stabilization of HIF. J Biol Chem 282: 4524-4532 (Pubitemid 47100953)
62. Kojima H, Gu H, Nomura S, Caldwell CC, Kobata T, Carmeliet P, Semenza GL, Sitkovsky MV (2002) Abnormal B lymphocyte development and autoimmunity in hypoxia-inducible factor 1alpha -deficient chimeric mice. Proc Natl Acad Sci USA 99: 2170-2174 (Pubitemid 34169033)
63. Kojima H, Kobayashi A, Sakurai D, Kanno Y, Hase H, Takahashi R, Totsuka Y, Semenza GL, Sitkovsky MV, Kobata T (2010) Differentiation stage-specific requirement in hypoxia-inducible factor-1alpha-regulated glycolytic pathway during murine B cell development in bone marrow. J Immunol 184: 154-163
64. 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 USA 101: 10440-10445 (Pubitemid 38924944)
65. Lando D, Peet DJ, Whelan DA, Gorman JJ, Whitelaw ML (2002) Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch. Science 295: 858-861 (Pubitemid 34118367)
66. Lee JS, Kim Y, Bhin J, Shin HJ, Nam HJ, Lee SH, Yoon JB, Binda O, Gozani O, Hwang D, Baek SH (2011) Hypoxia-induced methylation of a pontin chromatin remodeling factor. Proc Natl Acad Sci USA 108: 13510-13515
67. Li L, Shen JJ, Bournat JC, Huang L, Chattopadhyay A, Li Z, Shaw C, Graham BH, Brown CW (2009) Activin signaling: effects on body composition and mitochondrial energy metabolism. Endocrinology 150: 3521-3529
68. Lim JH, Lee YM, Chun YS, Chen J, Kim JE, Park JW (2010) Sirtuin 1 modulates cellular responses to hypoxia by deacetylating hypoxia- inducible factor 1alpha. Mol Cell 38: 864-878
69. Lombard DB, Alt FW, Cheng HL, Bunkenborg J, Streeper RS, Mostoslavsky R, Kim J, Yancopoulos G, Valenzuela D, Murphy A, Yang Y, Chen Y, Hirschey MD, Bronson RT, Haigis M, Guarente LP, Farese Jr. RV, Weissman S, Verdin E, Schwer B (2007) Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Mol Cell Biol 27: 8807-8814
70. Louis NA, Hamilton KE, Canny G, Shekels LL, Ho SB, Colgan SP (2006) Selective induction of mucin-3 by hypoxia in intestinal epithelia. J Cell Biochem 99: 1616-1627 (Pubitemid 44845721)
71. Luo W, Hu H, Chang R, Zhong J, Knabel M, O'Meally R, Cole RN, Pandey A, Semenza GL (2011) Pyruvate kinase M2 is a PHD3- stimulated coactivator for hypoxia-inducible factor 1. Cell 145: 732-744
72. 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 (Pubitemid 34984738)
73. Mandal S, Lindgren AG, Srivastava AS, Clark AT, Banerjee U (2011) Mitochondrial function controls proliferation and early differentiation potential of embryonic stem cells. Stem Cells 29: 486-495
74. Mansfield KD, Guzy RD, Pan Y, Young RM, Cash TP, Schumacker PT, Simon MC (2005) Mitochondrial dysfunction resulting from loss of cytochrome c impairs cellular oxygen sensing and hypoxic HIF-alpha activation. Cell Metab 1: 393-399 (Pubitemid 43960625)
75. Masson N, Singleton RS, Sekirnik R, Trudgian DC, Ambrose LJ, Miranda MX, Tian YM, Kessler BM, Schofield CJ, Ratcliffe PJ (2012) The FIH hydroxylase is a cellular peroxide sensor that modulates HIF transcriptional activity. EMBO Rep 13: 251-257
76. Masson N, Willam C, Maxwell PH, Pugh CW, Ratcliffe PJ (2001) Independent function of two destruction domains in hypoxiainducible factor-alpha chains activated by prolyl hydroxylation. EMBO J 20: 5197-5206 (Pubitemid 32910914)
77. Maxwell PH, Wiesener MS, Chang GW, Clifford SC, Vaux EC, Cockman ME, Wykoff CC, Pugh CW, Maher ER, Ratcliffe PJ (1999) The tumour suppressor protein VHL targets hypoxiainducible factors for oxygen-dependent proteolysis. Nature 399: 271-275 (Pubitemid 29246458)
78. Maynard MA, Qi H, Chung J, Lee EH, Kondo Y, Hara S, Conaway RC, Conaway JW, Ohh M (2003) Multiple splice variants of the human HIF-3 alpha locus are targets of the von Hippel-Lindau E3 ubiquitin ligase complex. J Biol Chem 278: 11032-11040 (Pubitemid 36792653)
79. Meister M (2004) Blood cells of Drosophila: cell lineages and role in host defence. Curr Opin Immunol 16: 10-15
80. Mukherjee T, Kim WS, Mandal L, Banerjee U (2011) Interaction between Notch and Hif-alpha in development and survival of Drosophila blood cells. Science 332: 1210-1213
81. Nakamura H, Makino Y, Okamoto K, Poellinger L, Ohnuma K, Morimoto C, Tanaka H (2005) TCR engagement increases hypoxia-inducible factor-1 alpha protein synthesis via rapamycinsensitive pathway under hypoxic conditions in human peripheral T cells. J Immunol 174: 7592-7599 (Pubitemid 40806263)
82. Nichols J, Smith A (2009) Naive and primed pluripotent states. Cell Stem Cell 4: 487-492
83. Nizet V, Johnson RS (2009) Interdependence of hypoxic and innate immune responses. Nat Rev Immunol 9: 609-617
84. O'Rourke JF, Tian YM, Ratcliffe PJ, Pugh CW (1999) Oxygenregulated and transactivating domains in endothelial PAS protein 1: comparison with hypoxia-inducible factor-1alpha. J Biol Chem 274: 2060-2071
85. Oberkofler H, Iglseder B, Klein K, Unger J, Haltmayer M, Krempler F, Paulweber B, Patsch W (2005) Associations of the UCP2 gene locus with asymptomatic carotid atherosclerosis in middle-aged women. Arterioscler Thromb Vasc Biol 25: 604-610 (Pubitemid 40315685)
86. Ohh M, Park CW, Ivan M, Hoffman MA, Kim TY, Huang LE, Pavletich N, Chau V, Kaelin WG (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
87. Pan Y, Mansfield KD, Bertozzi CC, Rudenko V, Chan DA, Giaccia AJ, Simon MC (2007) Multiple factors affecting cellular redox status and energy metabolism modulate hypoxia-inducible factor prolyl hydroxylase activity in vivo and in vitro. Mol Cell Biol 27: 912-925 (Pubitemid 46174556)
88. Peyssonnaux C, Cejudo-Martin P, Doedens A, Zinkernagel AS, Johnson RS, Nizet V (2007) Cutting edge: essential role of hypoxia inducible factor-1alpha in development of lipopolysaccharide- induced sepsis. J Immunol 178: 7516-7519 (Pubitemid 46898018)
89. Peyssonnaux C, Datta V, Cramer T, Doedens A, Theodorakis EA, Gallo RL, Hurtado-Ziola N, Nizet V, Johnson RS (2005) HIF- 1alpha expression regulates the bactericidal capacity of phagocytes. J Clin Invest 115: 1806-1815 (Pubitemid 40979719)
90. Pistollato F, Rampazzo E, Persano L, Abbadi S, Frasson C, Denaro L, D'Avella D, Panchision DM, Della Puppa A, Scienza R, Basso G (2010) Interaction of hypoxia-inducible factor-1alpha and Notch signaling regulates medulloblastoma precursor proliferation and fate. Stem Cells 28: 1918-1929
91. 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 (Pubitemid 27184117)
92. Qiang L, Wu T, Zhang HW, Lu N, Hu R, Wang YJ, Zhao L, Chen FH, Wang XT, You QD, Guo QL (2012) HIF-1alpha is critical for hypoxia-mediated maintenance of glioblastoma stem cells by activating Notch signaling pathway. Cell Death Differ 19: 284-294
93. Qiu X, Brown K, Hirschey MD, Verdin E, Chen D (2010) Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation. Cell Metab 12: 662-667
94. Rebay I, Fleming RJ, Fehon RG, Cherbas L, Cherbas P, Artavanis- Tsakonas S (1991) Specific EGF repeats of Notch mediate interactions with Delta and Serrate: implications for Notch as a multifunctional receptor. Cell 67: 687-699 (Pubitemid 121001482)
95. Rius J, Guma M, Schachtrup C, Akassoglou K, Zinkernagel AS, Nizet V, Johnson RS, Haddad GG, Karin M (2008) NF-kappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha. Nature 453: 807-811 (Pubitemid 351793778)
96. Robinson A, Keely S, Karhausen J, Gerich ME, Furuta GT, Colgan SP (2008) Mucosal protection by hypoxia-inducible factor prolyl hydroxylase inhibition. Gastroenterology 134: 145-155 (Pubitemid 350309309)
97. Sahlgren C, Gustafsson MV, Jin S, Poellinger L, Lendahl U (2008) Notch signaling mediates hypoxia-induced tumor cell migration and invasion. Proc Natl Acad Sci USA 105: 6392-6397 (Pubitemid 351758356)
98. Sainson RC, Harris AL (2006) Hypoxia-regulated differentiation: let's step it up a Notch. Trends Mol Med 12: 141-143
99. Schofield CJ, Ratcliffe PJ (2004) Oxygen sensing by HIF hydroxylases. Nat Rev Mol Cell Biol 5: 343-354 (Pubitemid 38579472)
100. 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 (Pubitemid 32381779)
101. Semenza GL (1996) Transcriptional regulation by hypoxia-inducible factor 1 molecular mechanisms of oxygen homeostasis. Trends Cardiovasc Med 6: 151-157
102. 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
103. Shi LZ, Wang R, Huang G, Vogel P, Neale G, Green DR, Chi H (2011) HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J Exp Med 208: 1367-1376
104. Simsek T, Kocabas F, Zheng J, Deberardinis RJ, Mahmoud AI, Olson EN, Schneider JW, Zhang CC, Sadek HA (2010) The distinct metabolic profile of hematopoietic stem cells reflects their location in a hypoxic niche. Cell Stem Cell 7: 380-390
105. Someya S, Yu W, Hallowszzz WC, Xu J, Vann JM, Leeuwenburgh C, Tanokura M, Denu JM, Prolla TA (2010) Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction. Cell 143: 802-812
106. Sun Q, Chen X, Ma J, Peng H, Wang F, Zha X, Wang Y, Jing Y, Yang H, Chen R, Chang L, Zhang Y, Goto J, Onda H, Chen T, Wang MR, Lu Y, You H, Kwiatkowski D, Zhang H (2011) Mammalian target of rapamycin up-regulation of pyruvate kinase isoenzyme type M2 is critical for aerobic glycolysis and tumor growth. Proc Natl Acad Sci USA 108: 4129-4134
107. Taguchi A, Yanagisawa K, Tanaka M, Cao K, Matsuyama Y, Goto H, Takahashi T (2008) Identification of hypoxia-inducible factor-1 alpha as a novel target for miR-17-92 microRNA cluster. Cancer Res 68: 5540-5545
108. Takehara T, Teramura T, Onodera Y, Hamanishi C, Fukuda K (2011)Reduced oxygen concentration enhances conversion of embryonic stem cells to epiblast stem cells. Stem Cells Dev (advance online publication; doi:10.1089/scd.2011. 0322)
109. Takubo K, Goda N, Yamada W, Iriuchishima H, Ikeda E, Kubota Y, Shima H, Johnson RS, Hirao A, Suematsu M, Suda T (2010) Regulation of the HIF-1alpha level is essential for hematopoietic stem cells. Cell Stem Cell 7: 391-402
110. Tang H, Kambris Z, Lemaitre B, Hashimoto C (2006) Two proteases defining a melanization cascade in the immune system of Drosophila. J Biol Chem 281: 28097-28104 (Pubitemid 44414523)
111. Tao R, Coleman MC, Pennington JD, Ozden O, Park SH, Jiang H, Kim HS, Flynn CR, Hill S, Hayes McDonald W, Olivier AK, Spitz DR, Gius D (2010) Sirt3-mediated deacetylation of evolutionarily conserved lysine 122 regulates MnSOD activity in response to stress. Mol Cell 40: 893-904
112. Tesar PJ, Chenoweth JG, Brook FA, Davies TJ, Evans EP, Mack DL, Gardner RL, McKay RD (2007) New cell lines from mouse epiblast share defining features with human embryonic stem cells. Nature 448: 196-199 (Pubitemid 47067378)
113. Tissenbaum HA, Guarente L (2001) Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 410: 227-230 (Pubitemid 32216597)
114. Vallier L, Reynolds D, Pedersen RA (2004) Nodal inhibits differentiation of human embryonic stem cells along the neuroectodermal default pathway. Dev Biol 275: 403-421 (Pubitemid 40288095)
115. Wacker I, Sachs M, Knaup K, Wiesener M, Weiske J, Huber O, Akcetin Z, Behrens J (2009) Key role for activin B in cellular transformation after loss of the von Hippel-Lindau tumor suppressor. Mol Cell Biol 29: 1707-1718
116. Walmsley SR, Chilvers ER, Thompson AA, Vaughan K, Marriott HM, Parker LC, Shaw G, Parmar S, Schneider M, Sabroe I, Dockrell DH, Milo M, Taylor CT, Johnson RS, Pugh CW, Ratcliffe PJ, Maxwell PH, Carmeliet P, Whyte MK (2011) Prolyl hydroxylase 3 (PHD3) is essential for hypoxic regulation of neutrophilic inflammation in humans and mice. J Clin Invest 121: 1053-1063
117. Walmsley SR, Print C, Farahi N, Peyssonnaux C, Johnson RS, Cramer T, Sobolewski A, Condliffe AM, Cowburn AS, Johnson N, Chilvers ER (2005) Hypoxia-induced neutrophil survival is mediated by HIF-1alpha-dependent NF-kappaB activity. J Exp Med 201: 105-115 (Pubitemid 40130088)
118. 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 USA 92: 5510-5514
119. Wang R, Zhang YW, Zhang X, Liu R, Hong S, Xia K, Xia J, Zhang Z, Xu H (2006) Transcriptional regulation of APH-1A and increased gamma-secretase cleavage of APP and Notch by HIF-1 and hypoxia. FASEB J 20: 1275-1277
120. Wang Y, Roche O, Yan MS, Finak G, Evans AJ, Metcalf JL, Hast BE, Hanna SC, Wondergem B, Furge KA, Irwin MS, Kim WY, Teh BT, Grinstein S, Park M, Marsden PA, Ohh M (2009) Regulation of endocytosis via the oxygen-sensing pathway. Nat Med 15: 319-324
121. Wenger RH, Stiehl DP, Camenisch G (2005) Integration of oxygen signaling at the consensus HRE. Sci STKE 2005: re12
122. Wiley M, Sweeney KR, Chan DA, Brown KM, McMurtrey C, Howard EW, Giaccia AJ, Blader IJ (2010) Toxoplasma gondii activates hypoxia-inducible factor (HIF) by stabilizing the HIF-1alpha subunit via type I activin-like receptor kinase receptor signaling. J Biol Chem 285: 26852-26860
123. Wilkins SE, Hyvarinen J, Chicher J, Gorman JJ, Peet DJ, Bilton RL, Koivunen P (2009) Differences in hydroxylation and binding of Notch and HIF-1alpha demonstrate substrate selectivity for factor inhibiting HIF-1 (FIH-1). Int J Biochem Cell Biol 41: 1563-1571
124. Xenaki G, Ontikatze T, Rajendran R, Stratford IJ, Dive C, Krstic-Demonacos M, Demonacos C (2008) PCAF is an HIF-1alpha cofactor that regulates p53 transcriptional activity in hypoxia. Oncogene 27: 5785-5796
125. YangW, Xia Y, Ji H, Zheng Y, Liang J, HuangW, Gao X, Aldape K, Lu Z (2011) Nuclear PKM2 regulates beta-catenin transactivation upon EGFR activation. Nature 480: 118-122
126. Yun Z, Maecker HL, Johnson RS, Giaccia AJ (2002) Inhibition of PPAR gamma 2 gene expression by the HIF-1-regulated gene DEC1/Stra13: a mechanism for regulation of adipogenesis by hypoxia. Dev Cell 2: 331-341 (Pubitemid 34266118)
127. Zhang H, Gao P, Fukuda R, Kumar G, Krishnamachary B, Zeller KI, Dang CV, Semenza GL (2007) HIF-1 inhibits mitochondrial biogenesis and cellular respiration in VHL-deficient renal cell carcinoma by repression of C-MYC activity. Cancer Cell 11: 407-420 (Pubitemid 46670080)
128. Zhang J, Khvorostov I, Hong JS, Oktay Y, Vergnes L, Nuebel E, Wahjudi PN, Setoguchi K, Wang G, Do A, Jung HJ, McCaffery JM, Kurland IJ, Reue K, Lee WN, Koehler CM, Teitell MA (2011) UCP2 regulates energy metabolism and differentiation potential of human pluripotent stem cells. EMBO J 30: 4860-4873
129. Zheng X, Linke S, Dias JM, Gradin K, Wallis TP, Hamilton BR, Gustafsson M, Ruas JL, Wilkins S, Bilton RL, Brismar K, Whitelaw ML, Pereira T, Gorman JJ, Ericson J, Peet DJ, Lendahl U, Poellinger L (2008) Interaction with factor inhibiting HIF-1 defines an additional mode of cross-coupling between the Notch and hypoxia signaling pathways. Proc Natl Acad Sci USA 105: 3368-3373 (Pubitemid 351723559)
130. Zhong L, D'Urso A, Toiber D, Sebastian C, Henry RE, Vadysirisack DD, Guimaraes A, Marinelli B, Wikstrom JD, Nir T, Clish CB, Vaitheesvaran B, Iliopoulos O, Kurland I, Dor Y, Weissleder R, Shirihai OS, Ellisen LW, Espinosa JM, Mostoslavsky R (2010) The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1alpha. Cell 140: 280-293
131. Zhou W, Choi M, Margineantu D, Margaretha L, Hesson J, Cavanaugh C, Blau AC, Horwitz MS, Hockenbery D, Ware C, Ruohola-Baker H (2012) HIF1α induced switch from bivalent to exclusively glycolytic metabolism during ESC-to-EpiSC/hESC transition. EMBO J 31: 2103-2116