Interferon-alpha inhibits cyclin E- and cyclin D1-dependent CDK-2 kinase activity associated with RB protein and E2F in Daudi cells

Biochem Biophys Res Commun. 1994 Apr 15;200(1):522-8. doi: 10.1006/bbrc.1994.1479.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Burkitt Lymphoma
  • CDC2 Protein Kinase / metabolism
  • CDC2-CDC28 Kinases*
  • Carrier Proteins*
  • Cell Cycle / drug effects
  • Cell Cycle Proteins*
  • Cell Line
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases*
  • Cyclins / isolation & purification
  • Cyclins / metabolism*
  • DNA-Binding Proteins*
  • E2F Transcription Factors
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / pharmacology*
  • Protein Kinase Inhibitors*
  • Protein Kinases / isolation & purification
  • Protein-Serine-Threonine Kinases*
  • Recombinant Proteins
  • Retinoblastoma Protein / isolation & purification
  • Retinoblastoma Protein / metabolism*
  • Retinoblastoma-Binding Protein 1
  • Transcription Factor DP1
  • Transcription Factors / isolation & purification
  • Transcription Factors / metabolism*
  • Tumor Cells, Cultured

Substances

  • Carrier Proteins
  • Cell Cycle Proteins
  • Cyclins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • Interferon alpha-2
  • Interferon-alpha
  • Protein Kinase Inhibitors
  • Recombinant Proteins
  • Retinoblastoma Protein
  • Retinoblastoma-Binding Protein 1
  • Transcription Factor DP1
  • Transcription Factors
  • Protein Kinases
  • Protein-Serine-Threonine Kinases
  • CDC2 Protein Kinase
  • CDC2-CDC28 Kinases
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases