Rebecca Cook
Faculty Member
Last active: 4/15/2019

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).

Muraoka RS, Waltz SE, Degen SJ
Endocrinology. 1999 140 (1): 187-96

PMID: 9886825 · DOI:10.1210/endo.140.1.6441

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.

MeSH Terms (22)

Base Sequence Basic Helix-Loop-Helix Leucine Zipper Transcription Factors Cell Line CREB-Binding Protein DNA DNA-Binding Proteins Gene Expression Regulation Growth Substances Hepatocyte Growth Factor Hepatocyte Nuclear Factor 4 Humans Molecular Sequence Data Nuclear Proteins Phosphoproteins Promoter Regions, Genetic Protein Binding Proto-Oncogene Proteins Receptors, Retinoic Acid Repressor Proteins Trans-Activators Transcription Factors Tretinoin

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