Hypoxia-inducible factor 1-alpha

NameHypoxia-inducible factor 1-alpha
Synonyms
  • ARNT-interacting protein
  • Basic-helix-loop-helix-PAS protein MOP1
  • BHLHE78
  • Class E basic helix-loop-helix protein 78
  • HIF-1-alpha
  • Member of PAS protein 1
  • MOP1
  • PAS domain-containing protein 8
  • PASD8
Gene NameHIF1A
OrganismHuman
Amino acid sequence
>lcl|BSEQ0004663|Hypoxia-inducible factor 1-alpha
MEGAGGANDKKKISSERRKEKSRDAARSRRSKESEVFYELAHQLPLPHNVSSHLDKASVM
RLTISYLRVRKLLDAGDLDIEDDMKAQMNCFYLKALDGFVMVLTDDGDMIYISDNVNKYM
GLTQFELTGHSVFDFTHPCDHEEMREMLTHRNGLVKKGKEQNTQRSFFLRMKCTLTSRGR
TMNIKSATWKVLHCTGHIHVYDTNSNQPQCGYKKPPMTCLVLICEPIPHPSNIEIPLDSK
TFLSRHSLDMKFSYCDERITELMGYEPEELLGRSIYEYYHALDSDHLTKTHHDMFTKGQV
TTGQYRMLAKRGGYVWVETQATVIYNTKNSQPQCIVCVNYVVSGIIQHDLIFSLQQTECV
LKPVESSDMKMTQLFTKVESEDTSSLFDKLKKEPDALTLLAPAAGDTIISLDFGSNDTET
DDQQLEEVPLYNDVMLPSPNEKLQNINLAMSPLPTAETPKPLRSSADPALNQEVALKLEP
NPESLELSFTMPQIQDQTPSPSDGSTRQSSPEPNSPSEYCFYVDSDMVNEFKLELVEKLF
AEDTEAKNPFSTQDTDLDLEMLAPYIPMDDDFQLRSFDQLSPLESSSASPESASPQSTVT
VFQQTQIQEPTANATTTTATTDELKTVTKDRMEDIKILIASPSPTHIHKETTSATSSPYR
DTQSRTASPNRAGKGVIEQTEKSHPRSPNVLSVALSQRTTVPEEELNPKILALQNAQRKR
KMEHDGSLFQAVGIGTLLQQPDDHAATTSLSWKRVKGCKSSEQNGMEQKTIILIPSDLAC
RLLGQSMDESGLPQLTSYDCEVNAPIQGSRNLLQGEELLRALDQVN
Number of residues826
Molecular Weight92669.595
Theoretical pI4.97
GO Classification
Functions
  • transcription factor activity, sequence-specific DNA binding
  • transcription factor activity, RNA polymerase II transcription factor binding
  • protein heterodimerization activity
  • transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding
  • transcription factor binding
  • protein kinase binding
  • transcription factor activity, transcription factor binding
  • ubiquitin protein ligase binding
  • nuclear hormone receptor binding
  • enzyme binding
  • sequence-specific DNA binding
  • histone acetyltransferase binding
  • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding
  • Hsp90 protein binding
  • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding
Processes
  • positive regulation of chemokine production
  • axon transport of mitochondrion
  • regulation of transcription, DNA-templated
  • oxygen homeostasis
  • epithelial to mesenchymal transition
  • positive regulation of vascular endothelial growth factor production
  • positive regulation of transcription from RNA polymerase II promoter in response to hypoxia
  • positive regulation of transcription, DNA-templated
  • regulation of transcription from RNA polymerase II promoter in response to hypoxia
  • negative regulation of growth
  • neural crest cell migration
  • positive regulation of pri-miRNA transcription from RNA polymerase II promoter
  • positive regulation of transcription from RNA polymerase II promoter
  • positive regulation of receptor biosynthetic process
  • negative regulation of bone mineralization
  • positive regulation of endothelial cell proliferation
  • regulation of aerobic respiration
  • response to hypoxia
  • muscle cell cellular homeostasis
  • regulation of gene expression
  • outflow tract morphogenesis
  • cerebral cortex development
  • Notch signaling pathway
  • positive regulation of hormone biosynthetic process
  • heart looping
  • connective tissue replacement involved in inflammatory response wound healing
  • positive regulation of epithelial cell migration
  • positive regulation of vascular endothelial growth factor receptor signaling pathway
  • digestive tract morphogenesis
  • lactate metabolic process
  • mRNA transcription from RNA polymerase II promoter
  • signal transduction
  • visual learning
  • positive regulation of chemokine-mediated signaling pathway
  • angiogenesis
  • hypoxia-inducible factor-1alpha signaling pathway
  • cellular response to interleukin-1
  • positive regulation of glycolytic process
  • regulation of transcription from RNA polymerase II promoter in response to oxidative stress
  • embryonic hemopoiesis
  • positive regulation of erythrocyte differentiation
  • cartilage development
  • B-1 B cell homeostasis
  • dopaminergic neuron differentiation
  • positive regulation of mitophagy
  • intestinal epithelial cell maturation
  • cardiac ventricle morphogenesis
  • negative regulation of thymocyte apoptotic process
  • positive regulation of neuroblast proliferation
  • response to muscle activity
  • elastin metabolic process
  • positive regulation of nitric-oxide synthase activity
  • negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway
  • lactation
  • positive regulation of insulin secretion involved in cellular response to glucose stimulus
  • epithelial cell differentiation involved in mammary gland alveolus development
  • retina vasculature development in camera-type eye
  • negative regulation of reactive oxygen species metabolic process
  • cellular iron ion homeostasis
  • neural fold elevation formation
  • cellular response to hypoxia
  • negative regulation of mesenchymal cell apoptotic process
  • glucose homeostasis
  • embryonic placenta development
  • regulation of transforming growth factor beta2 production
  • positive regulation of angiogenesis
  • hemoglobin biosynthetic process
  • collagen metabolic process
  • negative regulation of TOR signaling
  • vascular endothelial growth factor production
Components
  • nuclear speck
  • cytoplasm
  • nucleus
  • transcription factor complex
  • motile cilium
  • RNA polymerase II transcription factor complex
  • cytosol
  • nucleoplasm
General FunctionUbiquitin protein ligase binding
Specific FunctionFunctions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. Activation requires recruitment of transcriptional coactivators such as CREBPB and EP300. Activity is enhanced by interaction with both, NCOA1 or NCOA2. Interaction with redox regulatory protein APEX seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDQ16665
UniProtKB Entry NameHIF1A_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0021673|Hypoxia-inducible factor 1-alpha (HIF1A)
ATGAGCTCCCAATGTCGGAGTTTGGAAAACAAATTTGTCTTTTTAAAAGAAGGTCTAGGA
AACTCAAAACCTGAAGAATTGGAAGAAATCAGAATAGAAAATGGTAGGATAAGTTCTGAA
CGTCGAAAAGAAAAGTCTCGAGATGCAGCCAGATCTCGGCGAAGTAAAGAATCTGAAGTT
TTTTATGAGCTTGCTCATCAGTTGCCACTTCCACATAATGTGAGTTCGCATCTTGATAAG
GCCTCTGTGATGAGGCTTACCATCAGCTATTTGCGTGTGAGGAAACTTCTGGATGCTGGT
GATTTGGATATTGAAGATGACATGAAAGCACAGATGAATTGCTTTTATTTGAAAGCCTTG
GATGGTTTTGTTATGGTTCTCACAGATGATGGTGACATGATTTACATTTCTGATAATGTG
AACAAATACATGGGATTAACTCAGTTTGAACTAACTGGACACAGTGTGTTTGATTTTACT
CATCCATGTGACCATGAGGAAATGAGAGAAATGCTTACACACAGAAATGGCCTTGTGAAA
AAGGGTAAAGAACAAAACACACAGCGAAGCTTTTTTCTCAGAATGAAGTGTACCCTAACT
AGCCGAGGAAGAACTATGAACATAAAGTCTGCAACATGGAAGGTATTGCACTGCACAGGC
CACATTCACGTATATGATACCAACAGTAACCAACCTCAGTGTGGGTATAAGAAACCACCT
ATGACCTGCTTGGTGCTGATTTGTGAACCCATTCCTCACCCATCAAATATTGAAATTCCT
TTAGATAGCAAGACTTTCCTCAGTCGACACAGCCTGGATATGAAATTTTCTTATTGTGAT
GAAAGAATTACCGAATTGATGGGATATGAGCCAGAAGAACTTTTAGGCCGCTCAATTTAT
GAATATTATCATGCTTTGGACTCTGATCATCTGACCAAAACTCATCATGATATGTTTACT
AAAGGACAAGTCACCACAGGACAGTACAGGATGCTTGCCAAAAGAGGTGGATATGTCTGG
GTTGAAACTCAAGCAACTGTCATATATAACACCAAGAATTCTCAACCACAGTGCATTGTA
TGTGTGAATTACGTTGTGAGTGGTATTATTCAGCACGACTTGATTTTCTCCCTTCAACAA
ACAGAATGTGTCCTTAAACCGGTTGAATCTTCAGATATGAAAATGACTCAGCTATTCACC
AAAGTTGAATCAGAAGATACAAGTAGCCTCTTTGACAAACTTAAGAAGGAACCTGATGCT
TTAACTTTGCTGGCCCCAGCCGCTGGAGACACAATCATATCTTTAGATTTTGGCAGCAAC
GACACAGAAACTGATGACCAGCAACTTGAGGAAGTACCATTATATAATGATGTAATGCTC
CCCTCACCCAACGAAAAATTACAGAATATAAATTTGGCAATGTCTCCATTACCCACCGCT
GAAACGCCAAAGCCACTTCGAAGTAGTGCTGACCCTGCACTCAATCAAGAAGTTGCATTA
AAATTAGAACCAAATCCAGAGTCACTGGAACTTTCTTTTACCATGCCCCAGATTCAGGAT
CAGACACCTAGTCCTTCCGATGGAAGCACTAGACAAAGTTCACCTGAGCCTAATAGTCCC
AGTGAATATTGTTTTTATGTGGATAGTGATATGGTCAATGAATTCAAGTTGGAATTGGTA
GAAAAACTTTTTGCTGAAGACACAGAAGCAAAGAACCCATTTTCTACTCAGGACACAGAT
TTAGACTTGGAGATGTTAGCTCCCTATATCCCAATGGATGATGACTTCCAGTTACGTTCC
TTCGATCAGTTGTCACCATTAGAAAGCAGTTCCGCAAGCCCTGAAAGCGCAAGTCCTCAA
AGCACAGTTACAGTATTCCAGCAGACTCAAATACAAGAACCTACTGCTAATGCCACCACT
ACCACTGCCACCACTGATGAATTAAAAACAGTGACAAAAGACCGTATGGAAGACATTAAA
ATATTGATTGCATCTCCATCTCCTACCCACATACATAAAGAAACTACTAGTGCCACATCA
TCACCATATAGAGATACTCAAAGTCGGACAGCCTCACCAAACAGAGCAGGAAAAGGAGTC
ATAGAACAGACAGAAAAATCTCATCCAAGAAGCCCTAACGTGTTATCTGTCGCTTTGAGT
CAAAGAACTACAGTTCCTGAGGAAGAACTAAATCCAAAGATACTAGCTTTGCAGAATGCT
CAGAGAAAGCGAAAAATGGAACATGATGGTTCACTTTTTCAAGCAGTAGGAATTGGAACA
TTATTACAGCAGCCAGACGATCATGCAGCTACTACATCACTTTCTTGGAAACGTGTAAAA
GGATGCAAATCTAGTGAACAGAATGGAATGGAGCAAAAGACAATTATTTTAATACCCTCT
GATTTAGCATGTAGACTGCTGGGGCAATCAATGGATGAAAGTGGATTACCACAGCTGACC
AGTTATGATTGTGAAGTTAATGCTCCTATACAAGGCAGCAGAAACCTACTGCAGGGTGAA
GAATTACTCAGAGCTTTGGATCAAGTTAACTGA
GenBank Gene IDU22431
GeneCard IDNot Available
GenAtlas IDHIF1A
HGNC IDHGNC:4910
Chromosome Location14
LocusNot Available
References
  1. Wang GL, Jiang BH, Rue EA, Semenza GL: Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5510-4. 7539918
  2. Hogenesch JB, Chan WK, Jackiw VH, Brown RC, Gu YZ, Pray-Grant M, Perdew GH, Bradfield CA: 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 Mar 28;272(13):8581-93. 9079689
  3. Iyer NV, Leung SW, Semenza GL: The human hypoxia-inducible factor 1alpha gene: HIF1A structure and evolutionary conservation. Genomics. 1998 Sep 1;52(2):159-65. 9782081
  4. Lukashev D, Sitkovsky M: Preferential expression of the novel alternative isoform I.3 of hypoxia-inducible factor 1alpha in activated human T lymphocytes. Hum Immunol. 2008 Jul;69(7):421-5. doi: 10.1016/j.humimm.2008.05.004. Epub 2008 Jun 11. 18638657
  5. Heilig R, Eckenberg R, Petit JL, Fonknechten N, Da Silva C, Cattolico L, Levy M, Barbe V, de Berardinis V, Ureta-Vidal A, Pelletier E, Vico V, Anthouard V, Rowen L, Madan A, Qin S, Sun H, Du H, Pepin K, Artiguenave F, Robert C, Cruaud C, Bruls T, Jaillon O, Friedlander L, Samson G, Brottier P, Cure S, Segurens B, Aniere F, Samain S, Crespeau H, Abbasi N, Aiach N, Boscus D, Dickhoff R, Dors M, Dubois I, Friedman C, Gouyvenoux M, James R, Madan A, Mairey-Estrada B, Mangenot S, Martins N, Menard M, Oztas S, Ratcliffe A, Shaffer T, Trask B, Vacherie B, Bellemere C, Belser C, Besnard-Gonnet M, Bartol-Mavel D, Boutard M, Briez-Silla S, Combette S, Dufosse-Laurent V, Ferron C, Lechaplais C, Louesse C, Muselet D, Magdelenat G, Pateau E, Petit E, Sirvain-Trukniewicz P, Trybou A, Vega-Czarny N, Bataille E, Bluet E, Bordelais I, Dubois M, Dumont C, Guerin T, Haffray S, Hammadi R, Muanga J, Pellouin V, Robert D, Wunderle E, Gauguet G, Roy A, Sainte-Marthe L, Verdier J, Verdier-Discala C, Hillier L, Fulton L, McPherson J, Matsuda F, Wilson R, Scarpelli C, Gyapay G, Wincker P, Saurin W, Quetier F, Waterston R, Hood L, Weissenbach J: The DNA sequence and analysis of human chromosome 14. Nature. 2003 Feb 6;421(6923):601-7. Epub 2003 Jan 1. 12508121
  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  7. Arany Z, Huang LE, Eckner R, Bhattacharya S, Jiang C, Goldberg MA, Bunn HF, Livingston DM: An essential role for p300/CBP in the cellular response to hypoxia. Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):12969-73. 8917528
  8. Jiang BH, Zheng JZ, Leung SW, Roe R, Semenza GL: Transactivation and inhibitory domains of hypoxia-inducible factor 1alpha. Modulation of transcriptional activity by oxygen tension. J Biol Chem. 1997 Aug 1;272(31):19253-60. 9235919
  9. Kallio PJ, Okamoto K, O'Brien S, Carrero P, Makino Y, Tanaka H, Poellinger L: Signal transduction in hypoxic cells: inducible nuclear translocation and recruitment of the CBP/p300 coactivator by the hypoxia-inducible factor-1alpha. EMBO J. 1998 Nov 16;17(22):6573-86. 9822602
  10. Huang LE, Gu J, Schau M, Bunn HF: Regulation of hypoxia-inducible factor 1alpha is mediated by an O2-dependent degradation domain via the ubiquitin-proteasome pathway. Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):7987-92. 9653127
  11. Ema M, Hirota K, Mimura J, Abe H, Yodoi J, Sogawa K, Poellinger L, Fujii-Kuriyama Y: 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. 1999 Apr 1;18(7):1905-14. 10202154
  12. Bhattacharya S, Michels CL, Leung MK, Arany ZP, Kung AL, Livingston DM: Functional role of p35srj, a novel p300/CBP binding protein, during transactivation by HIF-1. Genes Dev. 1999 Jan 1;13(1):64-75. 9887100
  13. Aso T, Yamazaki K, Aigaki T, Kitajima S: Drosophila von Hippel-Lindau tumor suppressor complex possesses E3 ubiquitin ligase activity. Biochem Biophys Res Commun. 2000 Sep 16;276(1):355-61. 11006129
  14. Tanimoto K, Makino Y, Pereira T, Poellinger L: Mechanism of regulation of the hypoxia-inducible factor-1 alpha by the von Hippel-Lindau tumor suppressor protein. EMBO J. 2000 Aug 15;19(16):4298-309. 10944113
  15. Carrero P, Okamoto K, Coumailleau P, O'Brien S, Tanaka H, Poellinger L: Redox-regulated recruitment of the transcriptional coactivators CREB-binding protein and SRC-1 to hypoxia-inducible factor 1alpha. Mol Cell Biol. 2000 Jan;20(1):402-15. 10594042
  16. Sutter CH, Laughner E, Semenza GL: Hypoxia-inducible factor 1alpha protein expression is controlled by oxygen-regulated ubiquitination that is disrupted by deletions and missense mutations. Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4748-53. 10758161
  17. Masson N, Willam C, Maxwell PH, Pugh CW, Ratcliffe PJ: Independent function of two destruction domains in hypoxia-inducible factor-alpha chains activated by prolyl hydroxylation. EMBO J. 2001 Sep 17;20(18):5197-206. 11566883
  18. Cho S, Choi YJ, Kim JM, Jeong ST, Kim JH, Kim SH, Ryu SE: Binding and regulation of HIF-1alpha by a subunit of the proteasome complex, PSMA7. FEBS Lett. 2001 Jun 1;498(1):62-6. 11389899
  19. Jaakkola P, Mole DR, Tian YM, Wilson MI, Gielbert J, Gaskell SJ, von Kriegsheim A, Hebestreit HF, Mukherji M, Schofield CJ, Maxwell PH, Pugh CW, Ratcliffe PJ: Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science. 2001 Apr 20;292(5516):468-72. Epub 2001 Apr 5. 11292861
  20. Jeong JW, Bae MK, Ahn MY, Kim SH, Sohn TK, Bae MH, Yoo MA, Song EJ, Lee KJ, Kim KW: Regulation and destabilization of HIF-1alpha by ARD1-mediated acetylation. Cell. 2002 Nov 27;111(5):709-20. 12464182
  21. 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 Jun 15;16(12):1466-71. 12080085
  22. Ivan M, Haberberger T, Gervasi DC, Michelson KS, Gunzler V, Kondo K, Yang H, Sorokina I, Conaway RC, Conaway JW, Kaelin WG Jr: Biochemical purification and pharmacological inhibition of a mammalian prolyl hydroxylase acting on hypoxia-inducible factor. Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13459-64. Epub 2002 Sep 26. 12351678
  23. Yasinska IM, Sumbayev VV: S-nitrosation of Cys-800 of HIF-1alpha protein activates its interaction with p300 and stimulates its transcriptional activity. FEBS Lett. 2003 Aug 14;549(1-3):105-9. 12914934
  24. Sumbayev VV, Budde A, Zhou J, Brune B: HIF-1 alpha protein as a target for S-nitrosation. FEBS Lett. 2003 Jan 30;535(1-3):106-12. 12560087
  25. Freedman SJ, Sun ZY, Kung AL, France DS, Wagner G, Eck MJ: Structural basis for negative regulation of hypoxia-inducible factor-1alpha by CITED2. Nat Struct Biol. 2003 Jul;10(7):504-12. 12778114
  26. Bae SH, Jeong JW, Park JA, Kim SH, Bae MK, Choi SJ, Kim KW: Sumoylation increases HIF-1alpha stability and its transcriptional activity. Biochem Biophys Res Commun. 2004 Nov 5;324(1):394-400. 15465032
  27. Qi H, Gervais ML, Li W, DeCaprio JA, Challis JR, Ohh M: Molecular cloning and characterization of the von Hippel-Lindau-like protein. Mol Cancer Res. 2004 Jan;2(1):43-52. 14757845
  28. Li Z, Wang D, Messing EM, Wu G: VHL protein-interacting deubiquitinating enzyme 2 deubiquitinates and stabilizes HIF-1alpha. EMBO Rep. 2005 Apr;6(4):373-8. 15776016
  29. Arnesen T, Kong X, Evjenth R, Gromyko D, Varhaug JE, Lin Z, Sang N, Caro J, Lillehaug JR: Interaction between HIF-1 alpha (ODD) and hARD1 does not induce acetylation and destabilization of HIF-1 alpha. FEBS Lett. 2005 Nov 21;579(28):6428-32. Epub 2005 Nov 2. 16288748
  30. Fath DM, Kong X, Liang D, Lin Z, Chou A, Jiang Y, Fang J, Caro J, Sang N: Histone deacetylase inhibitors repress the transactivation potential of hypoxia-inducible factors independently of direct acetylation of HIF-alpha. J Biol Chem. 2006 May 12;281(19):13612-9. Epub 2006 Mar 15. 16543236
  31. Choi SM, Choi KO, Park YK, Cho H, Yang EG, Park H: Clioquinol, a Cu(II)/Zn(II) chelator, inhibits both ubiquitination and asparagine hydroxylation of hypoxia-inducible factor-1alpha, leading to expression of vascular endothelial growth factor and erythropoietin in normoxic cells. J Biol Chem. 2006 Nov 10;281(45):34056-63. Epub 2006 Sep 13. 16973622
  32. Berta MA, Mazure N, Hattab M, Pouyssegur J, Brahimi-Horn MC: SUMOylation of hypoxia-inducible factor-1alpha reduces its transcriptional activity. Biochem Biophys Res Commun. 2007 Aug 31;360(3):646-52. Epub 2007 Jun 27. 17610843
  33. Carbia-Nagashima A, Gerez J, Perez-Castro C, Paez-Pereda M, Silberstein S, Stalla GK, Holsboer F, Arzt E: RSUME, a small RWD-containing protein, enhances SUMO conjugation and stabilizes HIF-1alpha during hypoxia. Cell. 2007 Oct 19;131(2):309-23. 17956732
  34. Liu YV, Baek JH, Zhang H, Diez R, Cole RN, Semenza GL: RACK1 competes with HSP90 for binding to HIF-1alpha and is required for O(2)-independent and HSP90 inhibitor-induced degradation of HIF-1alpha. Mol Cell. 2007 Jan 26;25(2):207-17. 17244529
  35. Paltoglou S, Roberts BJ: HIF-1alpha and EPAS ubiquitination mediated by the VHL tumour suppressor involves flexibility in the ubiquitination mechanism, similar to other RING E3 ligases. Oncogene. 2007 Jan 25;26(4):604-9. Epub 2006 Aug 21. 16862177
  36. Kim EJ, Yoo YG, Yang WK, Lim YS, Na TY, Lee IK, Lee MO: Transcriptional activation of HIF-1 by RORalpha and its role in hypoxia signaling. Arterioscler Thromb Vasc Biol. 2008 Oct;28(10):1796-802. doi: 10.1161/ATVBAHA.108.171546. Epub 2008 Jul 24. 18658046
  37. Yee Koh M, Spivak-Kroizman TR, Powis G: HIF-1 regulation: not so easy come, easy go. Trends Biochem Sci. 2008 Nov;33(11):526-34. doi: 10.1016/j.tibs.2008.08.002. Epub 2008 Sep 21. 18809331
  38. Nardinocchi L, Puca R, Guidolin D, Belloni AS, Bossi G, Michiels C, Sacchi A, Onisto M, D'Orazi G: Transcriptional regulation of hypoxia-inducible factor 1alpha by HIPK2 suggests a novel mechanism to restrain tumor growth. Biochim Biophys Acta. 2009 Feb;1793(2):368-77. doi: 10.1016/j.bbamcr.2008.10.013. Epub 2008 Nov 6. 19046997
  39. Li Y, Lim S, Hoffman D, Aspenstrom P, Federoff HJ, Rempe DA: HUMMR, a hypoxia- and HIF-1alpha-inducible protein, alters mitochondrial distribution and transport. J Cell Biol. 2009 Jun 15;185(6):1065-81. doi: 10.1083/jcb.200811033. 19528298
  40. Gimm T, Wiese M, Teschemacher B, Deggerich A, Schodel J, Knaup KX, Hackenbeck T, Hellerbrand C, Amann K, Wiesener MS, Honing S, Eckardt KU, Warnecke C: Hypoxia-inducible protein 2 is a novel lipid droplet protein and a specific target gene of hypoxia-inducible factor-1. FASEB J. 2010 Nov;24(11):4443-58. doi: 10.1096/fj.10-159806. Epub 2010 Jul 12. 20624928
  41. Xu D, Yao Y, Lu L, Costa M, Dai W: Plk3 functions as an essential component of the hypoxia regulatory pathway by direct phosphorylation of HIF-1alpha. J Biol Chem. 2010 Dec 10;285(50):38944-50. doi: 10.1074/jbc.M110.160325. Epub 2010 Oct 1. 20889502
  42. Kalousi A, Mylonis I, Politou AS, Chachami G, Paraskeva E, Simos G: Casein kinase 1 regulates human hypoxia-inducible factor HIF-1. J Cell Sci. 2010 Sep 1;123(Pt 17):2976-86. doi: 10.1242/jcs.068122. Epub 2010 Aug 10. 20699359
  43. Bandau S, Knebel A, Gage ZO, Wood NT, Alexandru G: UBXN7 docks on neddylated cullin complexes using its UIM motif and causes HIF1alpha accumulation. BMC Biol. 2012 Apr 26;10:36. doi: 10.1186/1741-7007-10-36. 22537386
  44. Shan B, Gerez J, Haedo M, Fuertes M, Theodoropoulou M, Buchfelder M, Losa M, Stalla GK, Arzt E, Renner U: RSUME is implicated in HIF-1-induced VEGF-A production in pituitary tumour cells. Endocr Relat Cancer. 2012 Jan 9;19(1):13-27. doi: 10.1530/ERC-11-0211. Print 2012 Feb. 22009797
  45. Altun M, Zhao B, Velasco K, Liu H, Hassink G, Paschke J, Pereira T, Lindsten K: Ubiquitin-specific protease 19 (USP19) regulates hypoxia-inducible factor 1alpha (HIF-1alpha) during hypoxia. J Biol Chem. 2012 Jan 13;287(3):1962-9. doi: 10.1074/jbc.M111.305615. Epub 2011 Nov 29. 22128162
  46. Foxler DE, Bridge KS, James V, Webb TM, Mee M, Wong SC, Feng Y, Constantin-Teodosiu D, Petursdottir TE, Bjornsson J, Ingvarsson S, Ratcliffe PJ, Longmore GD, Sharp TV: The LIMD1 protein bridges an association between the prolyl hydroxylases and VHL to repress HIF-1 activity. Nat Cell Biol. 2012 Jan 29;14(2):201-8. doi: 10.1038/ncb2424. 22286099
  47. Gerez J, Fuertes M, Tedesco L, Silberstein S, Sevlever G, Paez-Pereda M, Holsboer F, Turjanski AG, Arzt E: In silico structural and functional characterization of the RSUME splice variants. PLoS One. 2013;8(2):e57795. doi: 10.1371/journal.pone.0057795. Epub 2013 Feb 28. 23469069
  48. Seo KS, Park JH, Heo JY, Jing K, Han J, Min KN, Kim C, Koh GY, Lim K, Kang GY, Uee Lee J, Yim YH, Shong M, Kwak TH, Kweon GR: SIRT2 regulates tumour hypoxia response by promoting HIF-1alpha hydroxylation. Oncogene. 2015 Mar 12;34(11):1354-62. doi: 10.1038/onc.2014.76. Epub 2014 Mar 31. 24681946
  49. Kumar P, Gullberg U, Olsson I, Ajore R: Myeloid translocation gene-16 co-repressor promotes degradation of hypoxia-inducible factor 1. PLoS One. 2015 May 14;10(5):e0123725. doi: 10.1371/journal.pone.0123725. eCollection 2015. 25974097
  50. Michel G, Minet E, Ernest I, Roland I, Durant F, Remacle J, Michiels C: A model for the complex between the hypoxia-inducible factor-1 (HIF-1) and its consensus DNA sequence. J Biomol Struct Dyn. 2000 Oct;18(2):169-79. 11089639
  51. Elkins JM, Hewitson KS, McNeill LA, Seibel JF, Schlemminger I, Pugh CW, Ratcliffe PJ, Schofield CJ: Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1 alpha. J Biol Chem. 2003 Jan 17;278(3):1802-6. Epub 2002 Nov 21. 12446723
  52. Freedman SJ, Sun ZY, Poy F, Kung AL, Livingston DM, Wagner G, Eck MJ: Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1 alpha. Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5367-72. 11959990
  53. Dames SA, Martinez-Yamout M, De Guzman RN, Dyson HJ, Wright PE: Structural basis for Hif-1 alpha /CBP recognition in the cellular hypoxic response. Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5271-6. 11959977
  54. Min JH, Yang H, Ivan M, Gertler F, Kaelin WG Jr, Pavletich NP: Structure of an HIF-1alpha -pVHL complex: hydroxyproline recognition in signaling. Science. 2002 Jun 7;296(5574):1886-9. Epub 2002 May 9. 12004076
  55. Hon WC, Wilson MI, Harlos K, Claridge TD, Schofield CJ, Pugh CW, Maxwell PH, Ratcliffe PJ, Stuart DI, Jones EY: Structural basis for the recognition of hydroxyproline in HIF-1 alpha by pVHL. Nature. 2002 Jun 27;417(6892):975-8. Epub 2002 Jun 5. 12050673