CELL-CYCLE PROGRESSION IN MONKEY CELLS EXPRESSING SIMIAN-VIRUS-40 SMALL T-ANTIGEN FROM ADENOVIRUS VECTORS

The simian virus 40 small t antigen (small-t) is required for optimal viral replication and transformation, especially during the infection of nondividing cells, suggesting that the function of small-t is to pr omote cell cycle progression. The mechanism through which small-t prom otes cell growth reflects, in part, its binding and inhibition of prot ein phosphatase 2A (PP2A). The use of recombinant adenoviruses allows smalI-t expression in a majority of cells in a population, thus provid ing a convenient source of cells for biochemical analyses. In monkey k idney CV1 cells; small-t expressed from these adenovirus vectors activ ated the mitogen-activated protein kinase (MAPK) pathway, induced JNK activity, and increased AP-1 DNA-binding activity, all in a PP2A-depen dent manner. Expression of small-t also caused an increase in the phos phorylation of the Na+/H+ antiporter, a mitogen-activated ion exchange r whose activity correlates with its phosphorylation. At least part of the antiporter phosphorylation induced by small-t reflected activatio n of the MAPK pathway, as suggested by results of assays using a chemi cal inhibitor of the MAPK-activating kinase, MEK. Finally, small-t exp ression from adenovirus vectors promoted efficient cell cycle progress ion by growth-arrested cells. These vectors should facilitate further analysis of effects of small-t on cell cycle mediators.