Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/28217
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Type: Journal article
Title: Regulation of gene expression by the hypoxia-inducible factors
Author: Fedele, A.
Whitelaw, M.
Peet, D.
Citation: Molecular Interventions, 2002; 2(4):229-243
Publisher: American Society for Pharmacology and Experimental Therapeutics (ASPET)
Issue Date: 2002
ISSN: 1534-0384
1543-2548
Organisation: Centre for the Molecular Genetics of Development
Statement of
Responsibility: 
Anthony O. Fedele, Murray L. Whitelaw, and Daniel J. Peet
Abstract: Many molecular and physiological responses to hypoxia in mammals are controlled by the transcription factors Hypoxia-Inducible Factor-1α (HIF-1α) and HIF-2α. Their ability to promote the transcription of hypoxia-inducible genes is mediated by protein stability and regulation of a C-terminal transactivation domain. Oxygen-dependent hydroxylation of conserved proline and asparagine residues in HIF-α are required for targeting HIF-α to proteasomes for destruction, and for inhibiting its capacity for CBP/p300-dependent transactivation, respectively. In hypoxia, the O2 required for prolyl and asparaginyl hydroxylation is limiting, and HIF-α is thus stabilized and competent for transcription. Because these proteins participate in angiogenesis, glycolysis, programmed cell death, cancer, and ischemia, HIF-α and its mediators are attractive therapeutic targets.
Keywords: Animals; Humans; Oxygen; Procollagen-Proline Dioxygenase; Asparagine; Proline; Transcription, Genetic; Gene Expression Regulation; Aryl Hydrocarbon Receptor Nuclear Translocator; Basic Helix-Loop-Helix Transcription Factors; Von Hippel-Lindau Tumor Suppressor Protein; Hypoxia-Inducible Factor 1, alpha Subunit
Description: © 2002 American Society of Pharmacology and Experimental Therapeutics
RMID: 0020022555
DOI: 10.1124/mi.2.4.229
Published version: http://molinterv.aspetjournals.org/cgi/content/abstract/2/4/229
Appears in Collections:Molecular and Biomedical Science publications
Centre for the Molecular Genetics of Development publications

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