Kinases as Upstream Regulators of the HIF System: Their Emerging Potential as Anti-Cancer Drug Targets

Author(s): Elitsa Y. Dimova, Carine Michiels, Thomas Kietzmann

Journal Name: Current Pharmaceutical Design

Volume 15 , Issue 33 , 2009

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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

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Article Details

Year: 2009
Page: [3867 - 3877]
Pages: 11
DOI: 10.2174/138161209789649358
Price: $65

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