title: Interferon-alpha inhibits cyclin E- and cyclin D1-dependent CDK-2 kinase activity associated with RB protein and E2F in Daudi cells.
abstract: 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.
authors.affiliation: Department of Medicine, Pennsylvania State University College of Medicine, Hershey 17033.
authors.forename: K
authors.initials: K
authors.lastname: Zhang
authors.forename: R
authors.initials: R
authors.lastname: Kumar
mesh_terms: D002051:Burkitt Lymphoma; D016203:CDC2 Protein Kinase / Q000378:metabolism; D042846:CDC2-CDC28 Kinases; D002352:Carrier Proteins; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins; D002460:Cell Line; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D016213:Cyclins / Q000302:isolation & purification / Q000378:metabolism*; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000302:isolation & purification; D017346:Protein Serine-Threonine Kinases; D011994:Recombinant Proteins; D016160:Retinoblastoma Protein / Q000302:isolation & purification / Q000378:metabolism*; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000302:isolation & purification / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D016213:Cyclins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D047428:Protein Kinase Inhibitors; D011994:Recombinant Proteins; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases