Expression of hepatocyte growth factor-like protein is repressed by retinoic acid and enhanced by cyclic adenosine 3',5'-monophosphate response element-binding protein (CREB)-binding protein (CBP).
Endocrinology
; 140(1): 187-96, 1999 Jan.
Article
em En
| MEDLINE
| ID: mdl-9886825
ABSTRACT
In an effort to understand the molecular mechanisms involved in the regulation of expression of the gene encoding hepatocyte growth factor-like protein (HGFL), it was found that all-trans-retinoic acid dramatically represses expression of the endogenous HGFL gene in HepG2 cells, a human hepatocyte-derived cell line. This repression requires the sequence between nucleotides -135 and -105 in the 5'-flanking sequence of the HGFL gene, a site that has previously been shown to bind the transcription factor hepatocyte nuclear factor-4 (HNF-4). Electrophoretic mobility shift analysis suggests that the retinoic acid receptor does not bind to this site, and that retinoic acid does not alter binding of HNF-4 to this DNA site. However, the transcriptional coactivator, CREB-binding protein (CBP) coactivates expression of this gene through an indirect interaction with the HNF-4-binding site, and overexpression of CBP in HepG2 cells eliminates retinoic acid repression of reporter gene expression driven by the HGFL promoter. Overexpression of CBP also protects the endogenous HGFL gene from down-regulation by retinoic acid. These results suggest that HGFL gene expression requires CBP, and competition for limiting amounts of CBP by retinoic acid receptor may be a means of modifying the activity of HNF-4 at the HGFL gene promoter.
Buscar no Google
Bases de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
/
Tretinoína
/
Proteínas Nucleares
/
Transativadores
/
Regulação da Expressão Gênica
/
Proteínas Proto-Oncogênicas
/
Substâncias de Crescimento
/
Fator de Crescimento de Hepatócito
/
Proteínas de Ligação a DNA
Limite:
Humans
Idioma:
En
Revista:
Endocrinology
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Estados Unidos