Cell cycle regulator E2F1 modulates angiogenesis via p53-dependent transcriptional control of VEGF.
Proc Natl Acad Sci U S A
; 103(29): 11015-20, 2006 Jul 18.
Article
em En
| MEDLINE
| ID: mdl-16835303
ABSTRACT
The transcription factor E2F1 is known to regulate cell proliferation and has been thought to modulate tumorigenesis via this mechanism alone. Here we show that mice deficient in E2F1 exhibit enhanced angiogenesis. The proangiogenic phenotype in E2F1 deficiency is the result of overproduction of vascular endothelial growth factor (VEGF) and is prevented by VEGF blockade. Under hypoxic conditions, E2F1 down-regulates the expression of VEGF promoter activity by associating with p53 and specifically down-regulating expression of VEGF but not other hypoxia-inducible genes, suggesting a promoter structure context-dependent regulation mechanism. We found that the minimum VEGF promoter mediating transcriptional repression by E2F1 features an E2F1- binding site with four Sp-1 sites in close proximity. These data disclose an unexpected function of endogenous E2F1 regulation of angiogenic activity via p53-dependent transcriptional control of VEGF expression.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
/
Ciclo Celular
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Proteína Supressora de Tumor p53
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Fator A de Crescimento do Endotélio Vascular
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Fator de Transcrição E2F1
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article