Redox regulation of the hypoxia-inducible factor.
Reactive oxygen species (ROS) have long been considered only as cyto- and genotoxic. However, there is now compelling evidence that ROS also act as second messengers in response to various stimuli, such as growth factors, hormones and cytokines. The hypoxia-inducible transcription factor (HIF) is a master regulator of oxygen-sensitive gene expression. More recently, HIF has also been shown to respond to non-hypoxic stimuli. Interestingly, recent reports indicate that ROS regulate HIF stability and transcriptional activity in well-oxygenated cells, as well as under hypoxic conditions. Consequently, ROS appear to be key players in regulating HIF-dependent pathways under both normal and pathological circumstances. This review summarizes the current understanding of the role of ROS in the regulation of the mammalian HIF system.
Pouysségur
Jacques
J
Institute of Signaling, Developmental Biology and Cancer Research, CNRS UMR 6543, Centre A. Lacassagne, 33 Avenue Valombrose, F-06189 Nice, France.
Mechta-Grigoriou
Fatima
F
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D010100:Oxygen