Activation of a preexisting cellular factor as a basis for adenovirus E1A-mediated transcription control.

Transcription of the set of early adenovirus genes is subject to positive control by the viral E1A gene. For one early viral gene, the E2 gene, this induction involves an increase in a cellular promoter-specific factor termed E2F. We have analyzed the kinetics for this induction and find that E2F is present at only very low levels in extracts of uninfected cells or cells infected for up to 3 hr with adenovirus type 5. The factor increases rapidly at 5 hr and reaches a maximal level at 7-8 hr. The kinetics of induction of the factor are thus coincident with the induction of E2 transcription. The 13S E1A gene product (289-amino acid protein), which is required for the efficient activation of E2 transcription in a productive infection, is also responsible for the activation of E2F, because infection with mutant strain pm975 (13S+, 12S-) induces the factor, whereas no increase of E2F occurs in cells infected by mutant strain dl1500 (13S-, 12S+). Finally, increase in the factor does not involve synthesis of any new protein, because extracts prepared from cells infected with adenovirus type 5 and treated with cycloheximide from 1 hr after infection contain approximately the same level of E2F as extracts from infected but untreated cells. From these results, we conclude that activation of E2F, as a posttranslational event, is responsible for the stimulation of E2 transcription by E1A.