Transcriptional regulation of the rat vascular endothelial growth factor gene by hypoxia.
J Biol Chem
; 270(22): 13333-40, 1995 Jun 02.
Article
em En
| MEDLINE
| ID: mdl-7768934
ABSTRACT
Vascular endothelial growth factor (VEGF), a potent angiogenic factor and endothelial cell-specific mitogen, is up-regulated by hypoxia. However, the mechanism(s) responsible for hypoxic induction of VEGF has not been clearly delineated. We report that the steady state VEGF mRNA levels are increased 12 +/- 0.6-fold, but the transcriptional rate for VEGF is increased only 3.1 +/- 0.6-fold by hypoxia in PC12 cells. In order to investigate cis-regulatory sequences which mediate this response to hypoxia, we cloned the rat genomic sequences encoding VEGF and identified a 28-base pair element in the 5' promoter that mediates hypoxia-inducible transcription in transient expression assays. This element has sequence and protein binding similarities to the hypoxia-inducible factor 1 binding site within the erythropoietin 3' enhancer. Post-transcriptional mechanisms have also been suggested to play a role in the hypoxic induction of VEGF. Evidence is provided that a frequently used polyadenylation site is 1.9 kilobases downstream from the translation termination codon for rat VEGF. This site is 1.5 kilobases further downstream from the polyadenylation site previously reported for VEGF. This new finding reveals sequence motifs in the 3'-untranslated region that may mediate VEGF mRNA stability.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Hipóxia Celular
/
Regulação da Expressão Gênica
/
Fatores de Crescimento Endotelial
/
Linfocinas
Idioma:
En
Ano de publicação:
1995
Tipo de documento:
Article
País de afiliação:
Estados Unidos