Monkey cells synthesizing SV40 large T antigen were lysed and the extracts immunoprecipitated with either monoclonal anti-T antibody or monoclonal antibody to~ 110-114, the product of the retinoblastoma susceptibility gene (Rb). T and~ 110-114 coprecipitated in each case, implying that the proteins are complexed with each other. Substitution and internal deletion mutants of T that contain structural alterations in a ten residue, transformation-controlling domain failed to complex with~ 110-114. In contrast, T mutants bearing structural changes outside of this domain bound to~ 110-114. These results are consistent with a model for transformation by SV40 which, at least in part, involves T/p110-114 complex formation and the perturbation of Rb protein and/or T function.

The transforming region of the DNA tumor virus, SV40, encodes two proteins, the large (T) and small (t) tumor antigens. While both are active in the induction of a neoplastic phenotype in cultured cells, T, alone, is an obligatory participant in this process (Sleigh et al., 1978; Lewis and Martin, 1979; Kriegler et al., 1984; Brown et al., 1986; Jat et al., 1986; Bike1 et al., 1987). Indeed, it is clear that, when present in high enough concentration, T can perform all of the functions needed for either the transformation of established cells in culture or tumor formation in suitable rodents.