Transduction pathways involved in Hypoxia-Inducible Factor-1 phosphorylation and activation.
Hypoxia-Inducible Factor-1 (HIF-1) is a transcription factor which is activated by hypoxia and involved in the adaptative response of the cell to oxygen deprivation. During hypoxic stress, HIF-1 triggers the overexpression of genes coding for glycolytic enzymes and angiogenic factors. To be active HIF-1 must be phosphorylated. HIF-1 is a substrate for various kinase pathways including PI-3K and the MAP kinases ERK and p38. Several transduction pathways have been proposed which act downstream of putative oxygen sensors and lead to the activation of these kinases. In this review, we summarize some of the latest advances describing the possible signaling pathways leading to HIF-1 phosphorylation and subsequent activation. The physiological relevance of these regulations is also discussed.
Minet
E
E
Laboratoire de Biochimie et Biologie Cellulaire, Facultés Universitaires Notre-Dame de la Paix, 61 rue de Bruxelles, 5000 Namur, Belgium.
Michel
G
G
Mottet
D
D
Raes
M
M
Michiels
C
C
D020533:Angiogenesis Inhibitors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D014161:Transduction, Genetic
D020533:Angiogenesis Inhibitors; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D014157:Transcription Factors; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases