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https://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 |
DOI: | 10.1124/mi.2.4.229 |
Published version: | http://molinterv.aspetjournals.org/cgi/content/abstract/2/4/229 |
Appears in Collections: | Aurora harvest 6 Centre for the Molecular Genetics of Development publications Molecular and Biomedical Science publications |
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