INTERFERON-ALPHA INHIBITS CYCLIN E-DEPENDENT AND CYCLIN D1-DEPENDENT CDK-2 KINASE-ACTIVITY ASSOCIATED WITH RB PROTEIN AND E2F IN DAUDI CELLS

The state of phosphorylation of retinoblastoma (RB) protein is regulated by CDK2 and CDC2 kinases. In the studies presented here, we have investigated the effect of interferon-alpha (IFN-alpha) on cyclin-dependent kinases in Daudi cells which were synchronized at different points of the cell cycle progression. We observed that the IFN-alpha enhances the expression of underphosphorylated RB protein in Daudi cells released from the G1/S, and this was closely associated with the inhibition of CDK2 kinase and not CDC2 kinase activity. The observed IFN-alpha-sensitive CDK2 kinase activity was dependent on Cyclin E and cyclin D1 but not on cyclin A and was physically associated with transcriptional factors: RB and E2F. In addition, treatment of G1/S Daudi cells with IFN-alpha also inhibited the ability of CDK2 enzyme to phosphorylate the RB protein in vitro. These results suggest possible involvement of cell cycle kinases in IFN-alpha action. (C) 1994 Academic Press, Inc.