Transcriptional regulation of the Vascular Endothelial Growth Factor gene--a concert of activating factors.
The vascular endothelial growth factor A (VEGF-A) is essential during embryonic development as inactivation of only one allele of its gene results in embryonic lethality. Up-regulation of VEGF under physiological situations allows for adaptation to hypoxic stress, to transient inflammatory processes, and to wounding. Its expression also increases all along the process of neovascularization of solid and hematological tumors. The object of this article is to focus on the transcriptional regulation of its gene. The major cis-acting sequences and trans-activating factors will be described as well as the physiological and pathological situations leading to the intervention of such sequences and factors. We will also focus on two transcription factors essential to VEGF gene transcription: the hypoxia-inducible factor-1, which is responsible for its increased by hypoxia, as well as Sp1, which is implicated in the response to various extracellular stimuli.
Pagès
Gilles
G
Institute of Signaling, Developmental Biology and Cancer Research, CNRS-UMR 6543, Centre Antoine Lacassagne, 33 avenue de Valombrose, 06189 Nice cedex 2, France. gpages@unice.fr
Pouysségur
Jacques
J
D004268:DNA-Binding Proteins / Q000502:physiology; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins / Q000502:physiology; D011401:Promoter Regions, Genetic; D016329:Sp1 Transcription Factor / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology*; D042442:Vascular Endothelial Growth Factors / Q000235:genetics* / Q000502:physiology
D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D042442:Vascular Endothelial Growth Factors