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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- Boger D. L., Lee R. J., Bounaud P. Y., Meier P. Asymmetric synthesis of orthogonally protected L-threo-beta-hydroxyasparagine. J Org Chem. 2000 Oct 6;65(20):6770–6772. doi: 10.1021/jo000628s. [DOI] [PubMed] [Google Scholar]
- Bruick R. K., McKnight S. L. A conserved family of prolyl-4-hydroxylases that modify HIF. Science. 2001 Oct 11;294(5545):1337–1340. doi: 10.1126/science.1066373. [DOI] [PubMed] [Google Scholar]
- 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. doi: 10.1073/pnas.082121399. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Epstein A. C., Gleadle J. M., McNeill L. A., Hewitson K. S., O'Rourke J., Mole D. R., Mukherji M., Metzen E., Wilson M. I., Dhanda A. 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. doi: 10.1016/s0092-8674(01)00507-4. [DOI] [PubMed] [Google Scholar]
- 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. doi: 10.1073/pnas.082117899. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gronke R. S., Welsch D. J., VanDusen W. J., Garsky V. M., Sardana M. K., Stern A. M., Friedman P. A. Partial purification and characterization of bovine liver aspartyl beta-hydroxylase. J Biol Chem. 1990 May 25;265(15):8558–8565. [PubMed] [Google Scholar]
- 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. 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 May 31;277(29):26351–26355. doi: 10.1074/jbc.C200273200. [DOI] [PubMed] [Google Scholar]
- 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 5;417(6892):975–978. doi: 10.1038/nature00767. [DOI] [PubMed] [Google Scholar]
- Ivan M., Kondo K., Yang H., Kim W., Valiando J., Ohh M., Salic A., Asara J. M., Lane W. S., Kaelin W. G., Jr HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science. 2001 Apr 5;292(5516):464–468. doi: 10.1126/science.1059817. [DOI] [PubMed] [Google Scholar]
- Jaakkola P., Mole D. R., Tian Y. M., Wilson M. I., Gielbert J., Gaskell S. J., von Kriegsheim A., Hebestreit H. F., Mukherji M., Schofield C. J. Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science. 2001 Apr 5;292(5516):468–472. doi: 10.1126/science.1059796. [DOI] [PubMed] [Google Scholar]
- Jia S., VanDusen W. J., Diehl R. E., Kohl N. E., Dixon R. A., Elliston K. O., Stern A. M., Friedman P. A. cDNA cloning and expression of bovine aspartyl (asparaginyl) beta-hydroxylase. J Biol Chem. 1992 Jul 15;267(20):14322–14327. [PubMed] [Google Scholar]
- 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. doi: 10.1101/gad.991402. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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. doi: 10.1126/science.1068592. [DOI] [PubMed] [Google Scholar]
- Lavaissiere L., Jia S., Nishiyama M., de la Monte S., Stern A. M., Wands J. R., Friedman P. A. Overexpression of human aspartyl(asparaginyl)beta-hydroxylase in hepatocellular carcinoma and cholangiocarcinoma. J Clin Invest. 1996 Sep 15;98(6):1313–1323. doi: 10.1172/JCI118918. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mahon P. C., Hirota K., Semenza G. L. 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. doi: 10.1101/gad.924501. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Masson N., Willam C., Maxwell P. H., Pugh C. W., Ratcliffe P. J. 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. doi: 10.1093/emboj/20.18.5197. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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. doi: 10.1080/07391102.2000.10506656. [DOI] [PubMed] [Google Scholar]
- 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 May 9;296(5574):1886–1889. doi: 10.1126/science.1073440. [DOI] [PubMed] [Google Scholar]
- Przysiecki C. T., Staggers J. E., Ramjit H. G., Musson D. G., Stern A. M., Bennett C. D., Friedman P. A. 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. doi: 10.1073/pnas.84.22.7856. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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. doi: 10.1021/bi00487a018. [DOI] [PubMed] [Google Scholar]
- Semenza G. L. Regulation of mammalian O2 homeostasis by hypoxia-inducible factor 1. Annu Rev Cell Dev Biol. 1999;15:551–578. doi: 10.1146/annurev.cellbio.15.1.551. [DOI] [PubMed] [Google Scholar]
- Stenflo J., Holme E., Lindstedt S., Chandramouli N., Huang L. H., Tam J. P., Merrifield R. B. 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. doi: 10.1073/pnas.86.2.444. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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] [Google Scholar]
- Wang G. L., Jiang B. H., Rue E. A., Semenza G. L. 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. doi: 10.1073/pnas.92.12.5510. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yu F., White S. B., Zhao Q., Lee F. S. 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. doi: 10.1073/pnas.181341498. [DOI] [PMC free article] [PubMed] [Google Scholar]