Elitsa Y. Dimova, Carine Michiels and Thomas Kietzmann Pages 3867 - 3877 ( 11 )
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.
Phosphorylation,HIF-1,hypoxia,kinase,MAPK pathway,PI3K/PKB pathway
, , Department Chemistry/ Biochemistry, Erwin-Schrodinger Strasse 54, D-67663 Kaiserslautern, Germany.