Kinases as upstream regulators of the HIF system: their emerging potential as anti-cancer drug targets

Elitsa Y. Dimova, Carine Michiels, Thomas Kietzmann

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)3867-3877
Number of pages11
JournalCurrent Pharmaceutical Design
Volume15
Issue number33
DOIs
Publication statusPublished - Nov 2009

Keywords

  • HIF-1
  • Hypoxia
  • Kinase
  • MAPK pathway
  • Phosphorylation
  • PI3K/PKB pathway

Fingerprint

Dive into the research topics of 'Kinases as upstream regulators of the HIF system: their emerging potential as anti-cancer drug targets'. Together they form a unique fingerprint.

Cite this