Synergistic effect of cyclic AMP and insulin on the expression of cyclin A gene in Swiss 3T3 cells

Biochem Biophys Res Commun. 1998 Mar 27;244(3):843-8. doi: 10.1006/bbrc.1998.8362.

Abstract

Cyclic AMP and insulin exert a synergistic mitogenic effect on Swiss 3T3 cells. Here, we showed that the activity of cyclin A-dependent kinase was elevated 3-fold at 24 h after cotreatment of cells with dibutyryl cAMP and insulin. The cotreatment elevated cyclin A protein levels 12-fold higher than those of insulin-treated cells without altering the levels of CDK2 and p27Kip1 proteins. Interestingly, the half-life of cyclin A protein increased from 7 h in the insulin-treated cells to 22 h in the cotreated cells. Levels of cyclin A mRNA were also elevated 9-fold. Cotreatment synergistically increased the binding activities of transcription factors to the NF-Y and the E2F-like sites of the cyclin A promoter. However, neither NF-Y nor E2F was involved in the binding. These results suggest that the synergistic elevation of cyclin A protein may be achieved by both the stabilization of cyclin A protein and the recruitment of transcription factors to the NF-Y and E2F-like sites of the cyclin A promoter.

MeSH terms

  • 3T3 Cells
  • Animals
  • Bucladesine / pharmacology*
  • Cell Cycle / drug effects
  • Cyclin A / biosynthesis*
  • Cyclin A / genetics
  • Cyclin A / metabolism
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Enzyme Activation
  • Gene Expression Regulation
  • Half-Life
  • Insulin / pharmacology*
  • Mice
  • Mitogens / pharmacology*
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Kinases / metabolism
  • RNA, Messenger / analysis
  • Transcription Factors / metabolism

Substances

  • Cyclin A
  • Insulin
  • Mitogens
  • RNA, Messenger
  • Transcription Factors
  • Bucladesine
  • Protein Kinases