COMPLEX REGULATION OF THE ADENOVIRUS E2 PROMOTER BY THE VIRAL ONCOPROTEINS E1A AND E7 AND TUMOR-SUPPRESSOR RB

The adenovirus E2 gene promoter contains two positive regulatory eleme nts, the activating transcription factor (ATF) and E2 promoter binding factor (E2F) sites, in physical proximity which are important for ade novirus E1A-induced transcriptional activation of the E2 promoter. It is also known that E1A trans-activates through the E2F site by freeing E2F from inactive complexes containing E2F and tumor suppressor Rb or other proteins. In this study, we demonstrated that E1A, in addition to activating the E2F sites, could trans-activate the E2 promoter thro ugh enhancing the DNA binding ability of ATF; and enhanced ATF binding was phosphorylation-dependent. Besides, overexpression of Rb can bloc k both the transcriptional effect of E1A and human papillomavirus type 16 (HPV-16) E7, and E1A-induced ATF binding. Moreover, Rb can overcom e trans-activation through the E2F sites by E1A or E7. These data sugg est that E1A can trans-activate the E2 promoter through two regulatory elements by different mechanisms, and Rb can antagonize the trans-act ivation effect of E1A or E7.