Abstract
The hypoxia-inducible factor-1 (HIF-1) is a key regulator in the mammalian response to oxygen deficiency under both physiological and pathological conditions such as cancer. A number of studies indicated an association between tumor hypoxia, increased hypoxia-inducible factor (HIF-1α) levels and a poor prognosis. The HIF-1α regulation in response to hypoxia occurs primarily on the level of protein stability due to posttranslational hydroxylation. However, HIF α-subunits also respond to various growth factors, hormones, or cytokines under non-hypoxic conditions implicating the involvement of different kinase pathways in their regulation thereby increasing the interest in HIF-1α as a new drug target. Herein, we review current knowledge about phosphorylation-dependent HIF-1α regulation, HIF-1α protein-protein interactions and subcellular localization with emphasis on new therapeutic strategies targeting the HIF pathway. © 2009 Bentham Science Publishers Ltd.
Original language | English |
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Pages (from-to) | 3867-3877 |
Number of pages | 11 |
Journal | Current Pharmaceutical Design |
Volume | 15 |
Issue number | 33 |
DOIs | |
Publication status | Published - Nov 2009 |
Keywords
- HIF-1
- Hypoxia
- Kinase
- MAPK pathway
- Phosphorylation
- PI3K/PKB pathway