[Protein p53 inhibits the activity of the enhancer of the immediate-early genes of murine cytomegalovirus]

The protein encoded by the tumor suppressor gene p53 can complex and functionally interact with cytomegalovirus proteins produced during the immediate-early phase of infection. The functions of these complex are unclear but there is some evidence to suggest that binding of p53 to these viral proteins may inactivate p53 functions. Recent reports have shown that p53 is involved in regulation of transcription. In this study we have considered the possibility that p53 may regulate transcription of cytomegalovirus immediate early genes which play a crucial role for virus replication. Here we report that experiments in which NIH 3T3 cells were cotransfected with a p53 expression plasmid together with a reporter gene linked to the mouse cytomegalovirus immediate-early enhancer/promoter revealed that wild type p53 could efficiently reduce the transcriptional activity of this viral regulatory sequence. By contrast expression of a mutated p53 correlated with a much smaller reduction of transcription. Deletion mutants analysis of the enhancer revealed that repression of transcription by p53 requires a minimal promoter containing an SP1 consensus sequence and a TATA box.