Synergistic effect of cyclic AMP and insulin on the expression of cyclin A gene in Swiss 3T3 cells.
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.
Lee
Y H
YH
College of Pharmacy, Seoul National University, Korea.
Park
J S
JS
Park
C H
CH
Lee
S K
SK
D016475:3T3 Cells; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D019925:Cyclin A / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D006207:Half-Life; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D008934:Mitogens / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D014157:Transcription Factors / Q000378:metabolism
D019925:Cyclin A; D007328:Insulin; D008934:Mitogens; D012333:RNA, Messenger; D014157:Transcription Factors; D003994:Bucladesine; D011494:Protein Kinases