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Biochem J. Nov 1, 2002; 367(Pt 3): 571–575.
PMCID: PMC1222951

Hypoxia-inducible factor asparaginyl hydroxylase (FIH-1) catalyses hydroxylation at the beta-carbon of asparagine-803.

Abstract

Asparagine-803 in the C-terminal transactivation domain of human hypoxia-inducible factor (HIF)-1 alpha-subunit is hydroxylated by factor inhibiting HIF-1 (FIH-1) under normoxic conditions causing abrogation of the HIF-1alpha/p300 interaction. NMR and other analyses of a hydroxylated HIF fragment produced in vitro demonstrate that hydroxylation occurs at the beta-carbon of Asn-803 and imply production of the threo -isomer, in contrast with other known aspartic acid/asparagine hydroxylases that produce the erythro -isomer.

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Selected References

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  • Semenza GL. Regulation of mammalian O2 homeostasis by hypoxia-inducible factor 1. Annu Rev Cell Dev Biol. 1999;15:551–578. [PubMed]
  • 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):5510–5514. [PMC free article] [PubMed]
  • Lando David, Peet Daniel J, Whelan Dean A, Gorman Jeffrey J, Whitelaw Murray L. Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch. Science. 2002 Feb 1;295(5556):858–861. [PubMed]
  • 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):5197–5206. [PMC free article] [PubMed]
  • Epstein AC, Gleadle JM, McNeill LA, Hewitson KS, O'Rourke J, Mole DR, Mukherji M, Metzen E, Wilson MI, Dhanda A, et al. C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell. 2001 Oct 5;107(1):43–54. [PubMed]
  • Ivan M, Kondo K, Yang H, Kim W, Valiando J, Ohh M, Salic A, Asara JM, Lane WS, Kaelin WG., Jr HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science. 2001 Apr 20;292(5516):464–468. [PubMed]
  • Jaakkola P, Mole DR, Tian YM, Wilson MI, Gielbert J, Gaskell SJ, von Kriegsheim A, Hebestreit HF, Mukherji M, Schofield CJ, et al. Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science. 2001 Apr 20;292(5516):468–472. [PubMed]
  • Yu F, White SB, Zhao Q, Lee FS. HIF-1alpha binding to VHL is regulated by stimulus-sensitive proline hydroxylation. Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9630–9635. [PMC free article] [PubMed]
  • Bruick RK, McKnight SL. A conserved family of prolyl-4-hydroxylases that modify HIF. Science. 2001 Nov 9;294(5545):1337–1340. [PubMed]
  • Min Jung-Hyun, Yang Haifeng, Ivan Mircea, Gertler Frank, Kaelin William G, Jr, Pavletich Nikola P. Structure of an HIF-1alpha -pVHL complex: hydroxyproline recognition in signaling. Science. 2002 Jun 7;296(5574):1886–1889. [PubMed]
  • Hon Wai-Ching, Wilson Michael I, Harlos Karl, Claridge Timothy D W, Schofield Christopher J, Pugh Christopher W, Maxwell Patrick H, Ratcliffe Peter J, Stuart David I, Jones E Yvonne. Structural basis for the recognition of hydroxyproline in HIF-1 alpha by pVHL. Nature. 2002 Jun 27;417(6892):975–978. [PubMed]
  • Hewitson Kirsty S, McNeill Luke A, Riordan Madeline V, Tian Ya-Min, Bullock Alex N, Welford Richard W, Elkins Jonathan M, Oldham Neil J, Bhattacharya Shoumo, Gleadle Jonathan M, et al. Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural family. J Biol Chem. 2002 Jul 19;277(29):26351–26355. [PubMed]
  • Lando David, Peet Daniel J, Gorman Jeffrey J, Whelan Dean A, Whitelaw Murray L, Bruick Richard K. FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. Genes Dev. 2002 Jun 15;16(12):1466–1471. [PMC free article] [PubMed]
  • Mahon PC, Hirota K, Semenza GL. FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity. Genes Dev. 2001 Oct 15;15(20):2675–2686. [PMC free article] [PubMed]
  • Dames Sonja A, Martinez-Yamout Maria, De Guzman Roberto N, Dyson H Jane, Wright Peter E. 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):5271–5276. [PMC free article] [PubMed]
  • Freedman Steven J, Sun Zhen-Yu J, Poy Florence, Kung Andrew L, Livingston David M, Wagner Gerhard, Eck Michael J. 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):5367–5372. [PMC free article] [PubMed]
  • Stenflo J, Holme E, Lindstedt S, Chandramouli N, Huang LH, Tam JP, Merrifield RB. Hydroxylation of aspartic acid in domains homologous to the epidermal growth factor precursor is catalyzed by a 2-oxoglutarate-dependent dioxygenase. Proc Natl Acad Sci U S A. 1989 Jan;86(2):444–447. [PMC free article] [PubMed]
  • Lavaissiere L, Jia S, Nishiyama M, de la Monte S, Stern AM, Wands JR, Friedman PA. Overexpression of human aspartyl(asparaginyl)beta-hydroxylase in hepatocellular carcinoma and cholangiocarcinoma. J Clin Invest. 1996 Sep 15;98(6):1313–1323. [PMC free article] [PubMed]
  • Stenflo J. Structure-function relationships of epidermal growth factor modules in vitamin K-dependent clotting factors. Blood. 1991 Oct 1;78(7):1637–1651. [PubMed]
  • Przysiecki CT, Staggers JE, Ramjit HG, Musson DG, Stern AM, Bennett CD, Friedman PA. Occurrence of beta-hydroxylated asparagine residues in non-vitamin K-dependent proteins containing epidermal growth factor-like domains. Proc Natl Acad Sci U S A. 1987 Nov;84(22):7856–7860. [PMC free article] [PubMed]
  • Jia S, VanDusen WJ, Diehl RE, Kohl NE, Dixon RA, Elliston KO, Stern AM, Friedman PA. cDNA cloning and expression of bovine aspartyl (asparaginyl) beta-hydroxylase. J Biol Chem. 1992 Jul 15;267(20):14322–14327. [PubMed]
  • Boger DL, Lee RJ, Bounaud PY, Meier P. Asymmetric synthesis of orthogonally protected L-threo-beta-hydroxyasparagine. J Org Chem. 2000 Oct 6;65(20):6770–6772. [PubMed]
  • Selander M, Persson E, Stenflo J, Drakenberg T. 1H NMR assignment and secondary structure of the Ca2(+)-free form of the amino-terminal epidermal growth factor like domain in coagulation factor X. Biochemistry. 1990 Sep 4;29(35):8111–8118. [PubMed]
  • 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):169–179. [PubMed]
  • Gronke RS, Welsch DJ, VanDusen WJ, Garsky VM, Sardana MK, Stern AM, Friedman PA. Partial purification and characterization of bovine liver aspartyl beta-hydroxylase. J Biol Chem. 1990 May 25;265(15):8558–8565. [PubMed]

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