TRANSACTIVATION OF THE P53 ONCOGENE BY E1 A GENE-PRODUCTS

Infection of quiescent rat kidney cells with human adenovirus is shown to transcriptionally stimulate (transactivate) the p53 oncogene. The increased transcription results in an accumulation of p53-specific mRNA in parallel with an increase in p53 protein levels, although there is a considerable delay between transcriptional activation and the detection of stable p53 mRNA and protein. The induction of p53 is detectable with two monoclonal antibodies recognizing different epitopes. The induction of p53 by adenovirus is delayed compared to induction by serum, and it occurs after the onset of adenovirus-induced cellular DNA replication. Thus, adenovirus-induced DNA replication bypasses a G0 G1 control point. Experiments with hydroxyurea show that p53 activation does not require continued cell cycling and thus is likely to be a direct consequence of viral gene expression. Finally, the induction of p53 is shown to be dependent on expression of the 289-residue product encoded by the viral E1a gene. © 1990.