Title:
MECHANISM OF CONDITIONAL REGULATION OF THE HYPOXIA-INDUCIBLE FACTOR-1 BY THE VON HIPPEL-LINDAU TUMOR SUPPRESSOR PROTEIN
Document Type and Number:
WIPO Patent Application WO2002012326
Kind Code:
A3
Abstract:
Alterations to the transactivation (N-TAD) domain of HIF-1 alpha demonstrate this domain contains structures necessary for hypoxia-inducible transactivation, oxygen-dependent degradation, and VHL-HIF-1 alpha interaction. HIF-1 alpha sequences with alterations of the N-TAD domain, fragments and analogs thereof are useful in modifying or regulating the activity of bioentities. Agonists and antagonists of the N-TAD domain of HIF-1 alpha are also useful in modifying or regulating the activity of bioentities.
Inventors:
POELLINGER LORENZ
PEREIRA TERESA
RUAS JORGE
PEREIRA TERESA
RUAS JORGE
Application Number:
PCT/IB2001/001775
Publication Date:
August 28, 2003
Filing Date:
August 07, 2001
Export Citation:
Assignee:
ANGIOGENETICS SWEDEN AB (SE)
International Classes:
G01N33/50; A61K38/00; A61K45/00; A61P1/04; A61P1/16; A61P7/06; A61P9/00; A61P9/10; A61P13/12; A61P19/02; A61P29/00; A61P35/00; A61P43/00; C07K14/47; C12N1/15; C12N1/19; C12N1/21; C12N5/07; C12N5/09; C12N5/10; C12N15/09; C12P21/02; C12Q1/02; C12Q1/68; G01N33/15; G01N33/53; G01N33/566; (IPC1-7): C07K14/47; C07K14/435; A61K38/17; C12N5/06
Domestic Patent References:
| WO2000029437A1 | 2000-05-25 | |||
| WO1996039426A1 | 1996-12-12 |
Other References:
MAXWELL PATRICK H ET AL: "The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis.", NATURE (LONDON), vol. 399, no. 6733, 20 May 1999 (1999-05-20), pages 271 - 275, XP002207790, ISSN: 0028-0836
PUGH CHRISTOPHER W ET AL: "Activation of hypoxia-inducible factor-1;definition of regulatory domains within the alpha subunit.", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 272, no. 17, 1997, pages 11205 - 11214, XP002207791, ISSN: 0021-9258
SRINIVAS VICKRAM ET AL: "Characterization of an oxygen/redox-dependent degradation domain of hypoxia-inducible factor alpha (HIF-alpha) proteins.", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 260, no. 2, 5 July 1999 (1999-07-05), pages 557 - 561, XP002207792, ISSN: 0006-291X
SUTTER CARRIE HAYES ET AL: "Hypoxia-inducible factor 1alpha protein expression is controlled by oxygen-regulated ubiquitination that is disrupted by deletions and missense mutations.", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES, vol. 97, no. 9, 25 April 2000 (2000-04-25), April 25, 2000, pages 4748 - 4753, XP002207793, ISSN: 0027-8424
DATABASE EMBL 13 May 2000 (2000-05-13), IYER NV ET AL: "Hypoxia-inducible factor 1 alpha subunit", XP002207796
TANIMOTO KEIJI ET AL: "Mechanism of regulation of the hypoxia-inducible factor-1alpha by the von Hippel-Lindau tumor suppressor protein.", EMBO (EUROPEAN MOLECULAR BIOLOGY ORGANIZATION) JOURNAL, vol. 19, no. 16, 15 August 2000 (2000-08-15), pages 4298 - 4309, XP002207794, ISSN: 0261-4189
IVAN MIRCEA ET AL: "HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: Implications for O2 sensing.", SCIENCE (WASHINGTON D C), vol. 292, no. 5516, - 20 April 2001 (2001-04-20), pages 464 - 468, XP002207795, ISSN: 0036-8075
PUGH CHRISTOPHER W ET AL: "Activation of hypoxia-inducible factor-1;definition of regulatory domains within the alpha subunit.", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 272, no. 17, 1997, pages 11205 - 11214, XP002207791, ISSN: 0021-9258
SRINIVAS VICKRAM ET AL: "Characterization of an oxygen/redox-dependent degradation domain of hypoxia-inducible factor alpha (HIF-alpha) proteins.", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 260, no. 2, 5 July 1999 (1999-07-05), pages 557 - 561, XP002207792, ISSN: 0006-291X
SUTTER CARRIE HAYES ET AL: "Hypoxia-inducible factor 1alpha protein expression is controlled by oxygen-regulated ubiquitination that is disrupted by deletions and missense mutations.", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES, vol. 97, no. 9, 25 April 2000 (2000-04-25), April 25, 2000, pages 4748 - 4753, XP002207793, ISSN: 0027-8424
DATABASE EMBL 13 May 2000 (2000-05-13), IYER NV ET AL: "Hypoxia-inducible factor 1 alpha subunit", XP002207796
TANIMOTO KEIJI ET AL: "Mechanism of regulation of the hypoxia-inducible factor-1alpha by the von Hippel-Lindau tumor suppressor protein.", EMBO (EUROPEAN MOLECULAR BIOLOGY ORGANIZATION) JOURNAL, vol. 19, no. 16, 15 August 2000 (2000-08-15), pages 4298 - 4309, XP002207794, ISSN: 0261-4189
IVAN MIRCEA ET AL: "HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: Implications for O2 sensing.", SCIENCE (WASHINGTON D C), vol. 292, no. 5516, - 20 April 2001 (2001-04-20), pages 464 - 468, XP002207795, ISSN: 0036-8075
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