p53 and DNA polymerase α compete for binding to SV40 T antigen

Abstract

The large T antigen (T) of simian virus 40 is a multifunctional protein required for both viral DNA replication and cellular transformation¹. T antigen forms specific protein complexes with the host protein p53 in both virus-infected and transformed cells^2–4. p53 has recently been shown to be an oncogene^5–7, but its normal function is not clear. We previously established a radioim-munoassay⁸ to study the newly described complex between T antigen and DNA polymerase α, and have noted a similarity between the antigenic changes induced in T by the binding of both p53 and polymerase^9,10. We now extend this analysis to a larger collection of anti-T antibodies and formally establish that p53 and DNA polymerase α can compete for binding to the SV40 T antigen. At a critical concentration of the three components it is possible to detect a trimeric complex of T, p53 and DNA polymerase α. Our observations have important implications for the control by these nuclear oncogenes of viral and cellular DNA synthesis and viral host range in both normal and transformed cells. We present a model for the action of p53 in growth control.