Investigating the dependence of the hypoxia-inducible factor hydroxylases (factor inhibiting HIF and prolyl hydroxylase domain 2) on ascorbate and other reducing agents

Biochemical Journal

Volumn 427, Issue 1, 2010, Pages 135-142

  Flashman, Emily ^a   Davies, Sarah L ^a   Yeoh, Kar Kheng ^a   Schofield, Christopher J ^a,b  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b ReOx Ltd   (United Kingdom)

Author keywords

2 oxoglutarate; Ascorbate; Asparaginyl hydroxylase; Hypoxia inducible factor (HIF); Oxygenase; Prolyl hydroxylase

Indexed keywords

2-OXOGLUTARATE; ASPARAGINYL; HYDROXYLASES; HYPOXIA-INDUCIBLE FACTORS; OXYGENASES; PROLYL HYDROXYLASE;

CATALYSIS; ENZYMES; HYDROXYLATION;

REDUCING AGENTS;

3,4 DIHYDROXYPHENYLACETIC ACID; ANKYRIN; ASCORBIC ACID; ASCORBIC ACID 2 SULFATE; ASCORBIC ACID DERIVATIVE; ASPARAGINE; DEHYDROASCORBIC ACID; DITHIOTHREITOL; GLUTATHIONE; GULONIC GAMMA LACTONE; HYPOXIA INDUCIBLE FACTOR; HYPOXIA INDUCIBLE FACTOR 1ALPHA; ISOASCORBIC ACID; ISOPROPYLIDENE ASCORBIC ACID; PROCOLLAGEN PROLINE 2 OXOGLUTARATE 4 DIOXYGENASE; UNCLASSIFIED DRUG; 2 OXOGLUTARIC ACID; EGLN1 PROTEIN, HUMAN; HIF1A PROTEIN, HUMAN; PEPTIDE FRAGMENT; REDUCING AGENT;

ARTICLE; CATALYSIS; CONTROLLED STUDY; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME ANALYSIS; ENZYME MODIFICATION; ENZYME STRUCTURE; HUMAN; HYDROXYLATION; PRIORITY JOURNAL; PROTEIN DOMAIN; STIMULATION; STRUCTURE ANALYSIS; ANOXIA; CHEMISTRY; MASS SPECTROMETRY; METABOLISM;

ANKYRIN REPEAT; ANOXIA; ASCORBIC ACID; ASPARAGINE; HUMANS; HYDROXYLATION; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; KETOGLUTARIC ACIDS; PEPTIDE FRAGMENTS; PROCOLLAGEN-PROLINE DIOXYGENASE; REDUCING AGENTS; SPECTROMETRY, MASS, MATRIX-ASSISTED LASER DESORPTION-IONIZATION;

EID: 77950906905     PISSN: 02646021     EISSN: 14708728     Source Type: Journal    
DOI: 10.1042/BJ20091609     Document Type: Article

References (53)

1. Clifton, I. J., McDonough, M. A., Ehrismann, D., Kershaw, N. J., Granatino, N. and Schofield, C. J. (2006) Structural studies on 2-oxoglutarate oxygenases and related double-stranded β-helix fold proteins. J. Inorg. Biochem. 100, 644-669
2. Loenarz, C. and Schofield, C. J. (2008) Expanding chemical biology of 2-oxoglutarate oxygenases. Nat. Chem. Biol. 4, 152-156
3. Schofield, C. J. and Zhang, Z. H. (1999) Structural and mechanistic studies on 2-oxoglutarate-dependent oxygenases and related enzymes. Curr. Opin. Struct. Biol. 9, 722-731
4. Hausinger, R. P. (2004) Fe(II)/α-ketoglutarate-dependent hydroxylases and related enzymes. Crit. Rev. Biochem. Mol. 39, 21-68
5. Kivirikko, K. I. and Myllyharju, J. (1998) Prolyl 4-hydroxylases and their protein disulfide isomerase subunit. Matrix Biol. 16, 357-368
6. De Jong, L., Albracht, S. P. and Kemp, A. (1982) Prolyl 4-hydroxylase activity in relation to the oxidation state of enzyme-bound iron. The role of ascorbate in peptidyl proline hydroxylation. Biochim. Biophys. Acta 704, 326-332
7. De Jong, L. and Kemp, A. (1984) Stoicheiometry and kinetics of the prolyl 4-hydroxylase partial reaction. Biochim. Biophys. Acta 787, 105-111
8. Myllyla, R., Majamaa, K., Gunzler, V., Hanauskeabel, H. M. and Kivirikko, K. I. (1984) Ascorbate is consumed stoichiometrically in the uncoupled reactions catalyzed by prolyl 4-hydroxylase and lysyl hydroxylase. J. Biol. Chem. 259, 5403-5405
9. Semenza, G. L. and Wang, G. L. (1992) A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Mol. Cell. Biol. 12, 5447-5454
10. 2 tension. Proc. Natl. Acad. Sci. U.S.A. 92, 5510-5514
11. Bruick, R. K. and McKnight, S. L. (2001) A conserved family of prolyl-4-hydroxylases that modify HIF. Science 294, 1337-1340
12. Epstein, A. C. R., Gleadle, J. M., McNeill, L. A., Hewitson, K. S., O'Rourke, J., Mole, D. R., Mukherji, M., Metzen, E., Wilson, M. I., Dhanda, A. et al. (2001) C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell 107, 43-54
13. Hewitson, K. S., McNeill, L. A., Riordan, M. V., Tian, Y. M., Bullock, A. N., Welford, R. W. D., Elkins, J. M., Oldham, N. J., Battacharya, S., Gleadle, J. et al. (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
14. Taylor, M. S. (2001) Characterization and comparative analysis of the EGLN gene family. Gene 275, 125-132 (Pubitemid 32907334)
15. 2 sensing. Science 292, 464-468
16. 2-regulated prolyl hydroxylation. Science 292, 468-472
17. Lando, D., Peet, D. J., Whelan, D. A., Gorman, J. J. and Whitelaw, M. L. (2002) Asparagine hydroxylation of the HIF transactivation domain: A hypoxic switch. Science 295, 858-861
18. Kaelin, Jr, W. G. and Ratcliffe, P. J. (2008) Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol. Cell 30, 393-402
19. Schofield, C. J. and Ratcliffe, P. J. (2004) Oxygen sensing by HIF hydroxylases. Nat. Rev. Mol. Cell. Biol. 5, 343-354
20. Semenza, G. L. (2004) Hydroxylation of HIF-1: oxygen sensing at the molecular level. Physiology (Bethesda) 19, 176-182 (Pubitemid 39481932)
21. Hirsila, M., Koivunen, P., Gunzler, V., Kivirikko, K. I. and Myllyharju, J. (2003) Characterization of the human prolyl 4-hydroxylases that modify the hypoxia-inducible factor. J. Biol. Chem. 278, 30772-30780
22. McNeill, L. A., Flashman, E., Buck, M. R., Hewitson, K. S., Clifton, I. J., Jeschke, G., Claridge, T. D., Ehrismann, D., Oldham, N. J. and Schofield, C. J. (2005) Hypoxia-inducible factor prolyl hydroxylase 2 has a high affinity for ferrous iron and 2-oxoglutarate. Mol. Biosyst. 1, 321-324
23. Knowles, H. J., Raval, R. R., Harris, A. L. and Ratcliffe, P. J. (2003) Effect of ascorbate on the activity of hypoxia-inducible factor in cancer cells. Cancer Res. 63, 1764-1768 (Pubitemid 36460834)
24. Vissers, M. C. and Wilkie, R. P. (2007) Ascorbate deficiency results in impaired neutrophil apoptosis and clearance and is associated with up-regulation of hypoxia-inducible factor 1α. J. Leukoc. Biol. 81, 1236-1244
25. Page, E. L., Chan, D. A., Giaccia, A. J., Levine, M. and Richard, D. E. (2008) Hypoxia-inducible factor-1α stabilization in non-hypoxic conditions: role of oxidation and intracellular ascorbate depletion. Mol. Biol. Cell 19, 86-94
26. Salnikow, K., Donald, S. P., Bruick, R. K., Zhitkovich, A., Phang, J. M. and Kasprzak, K. S. (2004) Depletion of intracellular ascorbate by the carcinogenic metals nickel and cobalt results in the induction of hypoxic stress. J. Biol. Chem. 279, 40337-40344
27. Talks, K. L., Turley, H., Gatter, K. C., Maxwell, P. H., Pugh, C. W., Ratcliffe, P. J. and Harris, A. L. (2000) The expression and distribution of the hypoxia-inducible factors HIF-1α and HIF-2α in normal human tissues, cancers, and tumor-associated macrophages. Am. J. Pathol. 157, 411-421
28. Chen, Q., Espey, M. G., Sun, A. Y., Pooput, C., Kirk, K. L., Krishna, M. C., Khosh, D. B., Drisko, J. and Levine, M. (2008) Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Proc. Natl. Acad. Sci. U.S.A. 105, 11105-11109
29. Assouline, S. and Miller, W. H. (2006) High-dose vitamin C therapy: renewed hope or false promise? Can. Med. Assoc. J. 174, 956-957
30. Buettner, G. R. and Jurkiewicz, B. A. (1996) Catalytic metals, ascorbate and free radicals: combinations to avoid. Radiat. Res. 145, 532-541
31. Valko, M., Morris, H. and Cronin, M. T. (2005) Metals, toxicity and oxidative stress. Curr. Med. Chem. 12, 1161-1208
32. Welford, R. W. (2004) Studies on the DNA repair enzyme AlkB and the ascorbate dependence of the 2-oxoglutarate oxygenases, Ph.D. Thesis. University of Oxford, Oxford, U.K.
33. Berra, E., Benizri, E., Ginouves, A., Volmat, V., Roux, D. and Pouyssegur, J. (2003) HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1α in normoxia. EMBO J. 22, 4082-4090
34. Takeda, K., Cowan, A. and Fong, G. H. (2007) Essential role for prolyl hydroxylase domain protein 2 in oxygen homeostasis of the adult vascular system. Circulation 116, 774-781
35. Cockman, M. E., Webb, J. D., Kramer, H. B., Kessler, B. M. and Ratcliffe, P. J. (2009) Proteomics-based identification of novel factor inhibiting hypoxia-inducible factor (FIH) substrates indicates widespread asparaginyl hydroxylation of ankyrin repeat domain-containing proteins. Mol. Cell. Proteomics 8, 535-546
36. Linke, S., Hampton-Smith, R. J. and Peet, D. J. (2007) Characterization of ankyrin repeat-containing proteins as substrates of the asparaginyl hydroxylase factor inhibiting hypoxia-inducible transcription factor. Methods Enzymol. 435, 61-85
37. Hardy, A. P., Prokes, I., Kelly, L., Campbell, I. D. and Schofield, C. J. (2009) Asparaginyl β-hydroxylation of proteins containing ankyrin repeat domains influences their stability and function. J. Mol. Biol. 392, 994-1006
38. Kelly, L., McDonough, M. A., Coleman, M. L., Ratcliffe, P. J. and Schofield, C. J. (2009) Asparagine β-hydroxylation stabilizes the ankyrin repeat domain fold. Mol. Biosyst. 5, 52-58
39. Inaba, K. and Ito, K. (2002) Paradoxical redox properties of DsbB and DsbA in the protein disulfide-introducing reaction cascade. EMBO J. 21, 2646-2654
40. Rost, J. and Rapoport, S. (1964) Reduction-potential of glutathione. Nature 201, 185
41. Becker, D. (2008) Antioxidant molecules and redox cofactors. In Redox Biochemistry (Banerjee, R., ed.), Wiley, Chichester
42. Parra, C., Rodriguez, J., Baeza, J., Freer, J. and and Duran, N. (1998) Iron-binding catechols lignin and chlorolignin. Biochem. Biophys. Res. Commun. 251, 399-402
43. Rocklin, A. M., Tierney, D. L., Kofman, V., Brunhuber, N. M., Hoffman, B. M., Christoffersen, R. E., Reich, N. O., Lipscomb, J. D. and Que, Jr, L. (1999) Role of the nonheme Fe(II) center in the biosynthesis of the plant hormone ethylene. Proc. Natl. Acad. Sci. U.S.A. 96, 7905-7909
44. Lawrence, C. C., Sobey, W. J., Field, R. A., Baldwin, J. E. and Schofield, C. J. (1996) Purification and initial characterization of proline 4-hydroxylase from Streptomyces griseoviridus P8648: a 2-oxoacid, ferrous-dependent dioxygenase involved in etamycin biosynthesis. Biochem. J. 313, 185-191
45. Majamaa, K., Gunzler, V., Hanauske-Abel, H. M., Myllyla, R. and Kivirikko, K. I. (1986) Partial identity of the 2-oxoglutarate and ascorbate binding sites of prolyl 4-hydroxylase. J. Biol. Chem. 261, 7819-7823
46. Tschank, G., Sanders, J., Baringhaus, K. H., Dallacker, F., Kivirikko, K. I. and Gunzler, V. (1994) Structural requirements for the utilization of ascorbate analogues in the prolyl 4-hydroxylase reaction. Biochem. J. 300, 75-79 (Pubitemid 24151019)
47. Chowdhury, R., McDonough, M. A., Mecinovic, J., Loenarz, C., Flashman, E., Hewitson, K. S., Domene, C. and Schofield, C. J. (2009) Structural basis for binding of hypoxiainducible factor to the oxygen-sensing prolyl hydroxylases. Structure 17, 981-989
48. McDonough, M. A., Li, V., Flashman, E., Chowdhury, R., Mohr, C., Lienard, B. M., Zondlo, J., Oldham, N. J., Clifton, I. J., Lewis, J. et al. (2006) Cellular oxygen sensing: crystal structure of hypoxia-inducible factor prolyl hydroxylase (PHD2). Proc. Natl. Acad. Sci. U.S.A. 103, 9814-9819
49. McDonough, M. A., Kavanagh, K. L., Butler, D., Searls, T., Oppermann, U. and Schofield, C. J. (2005) Structure of human phytanoyl-CoA 2-hydroxylase identifies molecular mechanisms of Refsum disease. J. Biol. Chem. 280, 41101-41110
50. Meister, A. and Anderson, M. E. (1983) Glutathione. Annu. Rev. Biochem. 52, 711-760
51. Myllyla, R., Kuutti-Savolainen, E. R. and Kivirikko, K. I. (1978) The role of ascorbate in the prolyl hydroxylase reaction. Biochem. Biophys. Res. Commun. 83, 441-448
52. Coleman, M. L., McDonough, M. A., Hewitson, K. S., Coles, C., Mecinovic, J., Edelmann, M., Cook, K. M., Cockman, M. E., Lancaster, D. E., Kessler, B. M. et al. (2007) Asparaginyl hydroxylation of the Notch ankyrin repeat domain by factor inhibiting hypoxia-inducible factor. J. Biol. Chem. 282, 24027-24038
53. Hewitson, K. S., McNeill, L. A. and Schofield, C. J. (2004) Modulating the hypoxia-inducible factor signaling pathway: applications from cardiovascular disease to cancer. Curr. Pharm. Des. 10, 821-833