ACTIVATING-TRANSCRIPTION FACTOR-2 (ATF2) DOWN-REGULATES HEPATITIS-B-VIRUS-X PROMOTER ACTIVITY BY THE COMPETITION FOR THE ACTIVATING PROTEIN-I BINDING-SITE AND THE FORMATION OF THE ATF2-JUN-HETERODIMER

The hepatitis B viral X promoter is known to be positively autoregulat ed by its own HBx protein, which also interacts with many cellular reg ulatory proteins, We investigated the effect of activating transcripti on factor 2, (ATF2) on the activity of the PL promoter. Cotransfection of the ATF2 expression vector with a X promoter-chloramphenicol acety ltransferase plasmid repressed the X promoter activity in HepG2 cells, HBx activated activating protein 1 (AP-1)-mediated transcription thro ugh the hepatitis B virus E element by 35-fold, while its activation a ctivity was inhibited in the presence of ATF2, suggesting that ATF2 in hibited the autoactivation of X promoter by HBx and basal transcriptio n mediated by AP-1. Since the binding sites of AP-1 and ATF2 in the he patitis B virus E element overlap, the repression of X promoter activi ty by ATF2 is everted by the competition for the AP-1 binding site and the formation of the ATF2-Jun heterodimer as in the casa of the conse nsus AP-1 element. However, the small X promoter had a ATF2 binding si te and was activated by ATF2. These results suggest that the syntheses of X proteins are differentially regulated by ATF2.