Regulation of gene expression by oxygen: NF-kappaB and HIF-1, two extremes.
Aerobic life is dependent on molecular oxygen for ATP regeneration, but only possible in a narrow range of oxygen concentrations. Increased oxygen tension is toxic through the generation of reactive oxygen species (ROS), while a decrease in oxygen concentration impairs energy availability and, hence, cell viability. Cells have developed strategies to respond to changes in oxygen tension: specific systems detect excessive ROS and hypoxia, leading to the activation of specific transcription factors and expression of appropriate target genes. The aim of this review is to describe how hypoxia-inducible factor-1 (HIF-1) and nuclear factor-kappaB (NF-kappaB) are regulated and what could be the sensors to the changes in oxygen levels. Some of the physiological responses initiated by these transcription factors are also mentioned.
Michiels
Carine
C
Biochemistry and Cellular Biology Laboratory, University of Namur, Belgium. carine.michiels@fundp.ac.be
Minet
Emmanuel
E
Mottet
Denis
D
Raes
Martine
M
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D018496:Hyperoxia / Q000235:genetics / Q000378:metabolism; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008954:Models, Biological; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000494:pharmacology*; D014157:Transcription Factors
D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016328:NF-kappa B; D009687:Nuclear Proteins; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D010100:Oxygen