P53-transformation-related protein: kinetics of synthesis and accumulation in SV40-infected primary mouse kidney cell cultures.

During abortive infection of Go/G1-arrested primary baby mouse kidney (BMK) cell cultures with simian virus 40 (SV40), expression of the viral large T antigen is followed by a mitotic host response including the stimulation of host macromolecular synthesis and induction into the cell cycle of Go/G1-arrested cells. We performed an extensive study of the sequential events taking place after SV40 infection of confluent BMK cell cultures. This study comprised a detailed kinetic analysis of transcription, synthesis, and accumulation of p53, in conjunction with the time course of large T antigen synthesis and SV40-induced cellular DNA replication. The monoclonal antibodies used for specifically recognizing mouse p53 were PAb 421, PAb 122, PAb 246, PAb 248, and RA3-2C2. Our results consistently show that under our experimental conditions, the stimulation of p53 synthesis and the accumulation of p53 occur well after the onset of T antigen-induced cellular DNA replication. This relatively late activation of p53 expression appears to be controlled at a level other than transcription. In conclusion, we suggest that, at least in certain cases, T antigen's mitogenic potential is not dependent on its interaction with p53.