RELATIVE MITOGENIC ACTIVITIES OF WILD-TYPE AND RETINOBLASTOMA BINDING-DEFECTIVE SV40 T-ANTIGENS IN SERUM-DEPRIVED AND SENESCENT HUMAN-DIPLOID FIBROBLASTS

A novel gene transfer approach was used to investigate whether the ret inoblastoma (Rb)-binding domain of simian virus 40 (SV40) T antigen is required for efficient T antigen-mediated stimulation of DNA synthesi s is quiescent or senescent human embryo fibroblasts. In senescent cel ls, comparison between wild-type T antigen and a mutant defective in R b binding (Glu-107-->Lys) revealed the latter to have almost-equal-to 15-fold lower activity. In contrast, comparison of wild-type and Rb- T antigens in serum-deprived quiescent cells revealed a much smaller (1 .8-fold) difference. Surprisingly, an 18-fold differential could be in duced by treating quiescent cells with the differentiating agent sodiu m butyrate. These results suggest that the role of Rb in control of th e cell cycle is strongly dependent on the physiological state of the c ell and the mechanism of growth arrest.