S-PHASE INDUCTION BY ADENOVIRUS E1A REQUIRES ACTIVATION OF CDC25A TYROSINE PHOSPHATASE

Adenovirus EIA proteins can induce quiescent cells to enter S-phase an d also affect the expression of cellular genes including various cell cycle regulators. Here we show that human cdc25A, a tyrosine phosphata se involved in regulation of the G1/S-phase transition of the cell cyc le, is a target of the adenovirus E1A protein in virus-infected human fibroblasts, Expression of E1A in quiescent fibroblasts leads to a rap id increase in cdc25A phosphatase activity and also increases both cdc 25A and cyclin E gene expression. Inhibition of cdc25A function by ant ibody injection prevents virus-induced entry into S-phase. These resul ts indicate that induction of high levels of cdc25A and its potential positive regulator cyclin E mediates the ability of E1A to induce S-ph ase in the presence of antiproliferative signals.