Exp Mol Med.  2002 Nov;34(5):379-384.

C/EBP binding activity to site F of the rat GLUT2 glucose transporter gene promoter is attenuated by c-Jun in vitro

Affiliations
  • 1Department of Biochemistry and Molecular Biology, Institute of Genetic Science, Yonsei University College of Medicine, Seoul, Korea. yha111@yumc.yonsei.ac.kr

Abstract

The expression of the GLUT2 glucose transporter gene in liver is suppressed in cultured hepatoma cell lines and primary cultured hepatocytes. Earlier report showed that CCAAT/enhancer binding protein (C/EBP) regulates the promoter activity of the rat GLUT2 glucose transporter gene in liver cells. C/EBPa and C/EBPb activated the promoter activity by binding to at least two regions of the promoter and one of the C/EBP binding sites, named as site F, also has the AP-1 binding consensus. In this study, we investigated whether the AP-1 can influence on C/EBP binding to this site. The addition of recombinant c-Jun protein with liver extract caused the attenuation of C/EBP binding to site F with the appearance of a new shifted band. The shifted band was competed out with the addition of unlabeled AP-1 consensus oligonucleotide, indicating that c-Jun also can bind to site F. Another C/EBP site on GLUT2 promoter, site H, did not bind AP-1. Analysis of the DNA-protein complex revealed that C/EBP and c-Jun bind to site F in mutually exclusive manner rather than form heterodimeric complex with each other. From these results, it is suggested that the transcriptional activation of C/EBP may be influenced by c-Jun protein in certain status of the liver cells, such as acute phase response, as well as hepatocarcinogenesis.

Keyword

C/EBP; c-jun; DNA-protein binding; GLUT2 promoter; hepatocyte

MeSH Terms

Animals
Base Sequence
Binding Sites
CCAAT-Enhancer-Binding Proteins/*metabolism
Cell Nucleus/metabolism
Cells, Cultured
Liver/cytology/metabolism
Male
Molecular Sequence Data
Monosaccharide Transport Proteins/*genetics/metabolism
Promoter Regions (Genetics)/*physiology
Proto-Oncogene Proteins c-jun/genetics/*metabolism
Rats
Rats, Sprague-Dawley
Recombinant Proteins/genetics/metabolism
Transcription Factor AP-1/genetics/metabolism
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