Distinct amounts of polyomavirus large T antigen are required for different functions of the protein.

Many cellular and some virally coded proteins regulating key events in higher cells have been found to be multifunctional. One example of such a protein is the polyomavirus large T antigen, which is involved not only in viral DNA replication and gene expression but also in the induction of the S phase in host cells, in the immortalization of various cell types and in the transactivation of some cellular genes. We recently constructed cell lines in which T antigen was synthesized under the control of a hormone-inducible promoter. This allowed us to induce different concentrations of the protein in the cell and to investigate the levels of large T antigen required for replication, S-phase induction and transactivation of a growth-regulated promoter. We found that significantly higher concentrations of large T antigen are required for the replication function of the protein than for either S phase induction or transactivation. These observations for the first time provide clear evidence for a potential regulation of different functions of a pleiotropic protein by the amount of that protein produced in the cell.