Wild-Type p53 Enhances Efficiency of Simian Virus 40 Large-T-Antigen-Induced Cellular Transformation

Abstract

ABSTRACT Abortive infection of BALB/c mouse embryo fibroblasts differing in p53 gene status (p53 +/+ versus p53 −/ − ) with simian virus 40 (SV40) revealed a quantitatively and qualitatively decreased transformation efficiency in p53 −/− cells compared to p53 +/+ cells, suggesting a supportive effect of wild-type (wt) p53 in the SV40 transformation process. SV40 transformation efficiency also was low in immortalized p53 −/− BALB/c 10-1 cells but could be restored to approximately the level in immortalized p53 +/+ BALB/c 3T3 cells by reconstituting wt p53, but not mutant p53 (mutp53), expression. Stable expression of large T antigen (LT) in p53 +/+ 3T3 cells resulted in full transformation, while LT expression in p53 −/− 10-1 cells could not promote growth in suspension or in soft agar to a significant extent. The helper effect of wt p53 is mediated by its cooperation with LT and resides in the p53 N terminus, as an N-terminally truncated p53 (ΔNp53) could not rescue the p53-null phenotype. The p53 N terminus serves as a scaffold for recruiting transcriptional regulators like p300/CBP and Mdm2 into the LT-p53 complex. Consequently, LT affected global and specific gene expression in p53 +/+ cells significantly more than in p53 −/− cells. Our data suggest that recruitment of transcriptional regulators into the LT-p53 complex may help to modify cellular gene expression in response to the needs of cellular transformation.