Activating transcription factor 2 (ATF2) down-regulates hepatitis B virus X promoter activity by the competition for the activating protein 1 binding site and the formation of the ATF2-Jun heterodimer.
The hepatitis B viral X promoter is known to be positively autoregulated by its own HBx protein, which also interacts with many cellular regulatory proteins. We investigated the effect of activating transcription factor 2 (ATF2) on the activity of the X promoter. Cotransfection of the ATF2 expression vector with a X promoter-chloramphenicol acetyltransferase plasmid repressed the X promoter activity in HepG2 cells. HBx activated activating protein 1 (AP-1)-mediated transcription through the hepatitis B virus E element by 35-fold, while its activation activity was inhibited in the presence of ATF2, suggesting that ATF2 inhibited the autoactivation of X promoter by HBx and basal transcription mediated by AP-1. Since the binding sites of AP-1 and ATF2 in the hepatitis B virus E element overlap, the repression of X promoter activity by ATF2 is exerted by the competition for the AP-1 binding site and the formation of the ATF2-Jun heterodimer as in the case of the consensus AP-1 element. However, the small X promoter had a ATF2 binding site and was activated by ATF2. These results suggest that the syntheses of X proteins are differentially regulated by ATF2.
Choi
C Y
CY
Department of Molecular Biology and Research Center for Cell Differentiation, Seoul National University, Seoul 151-742, Korea.
Choi
B H
BH
Park
G T
GT
Rho
H M
HM
D051698:Activating Transcription Factor 2; D001665:Binding Sites; D001667:Binding, Competitive; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D019281:Dimerization; D015536:Down-Regulation; D004742:Enhancer Elements, Genetic / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D016350:Leucine Zippers; D011401:Promoter Regions, Genetic; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D017362:Cyclic AMP Response Element-Binding Protein; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors; D015500:Chloramphenicol O-Acetyltransferase