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.
Keywords: Phosphorylation, HIF-1, hypoxia, kinase, MAPK pathway, PI3K/PKB pathway
Current Pharmaceutical Design
Title: Kinases as Upstream Regulators of the HIF System: Their Emerging Potential as Anti-Cancer Drug Targets
Volume: 15 Issue: 33
Author(s): Elitsa Y. Dimova, Carine Michiels and Thomas Kietzmann
Affiliation:
Keywords: Phosphorylation, HIF-1, hypoxia, kinase, MAPK pathway, PI3K/PKB pathway
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.
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Cite this article as:
Dimova Y. Elitsa, Michiels Carine and Kietzmann Thomas, Kinases as Upstream Regulators of the HIF System: Their Emerging Potential as Anti-Cancer Drug Targets, Current Pharmaceutical Design 2009; 15 (33) . https://dx.doi.org/10.2174/138161209789649358
DOI https://dx.doi.org/10.2174/138161209789649358 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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