Mevalonate deprivation alters the induction of fos and myc by growth factors.
Besides cholesterol, mevalonate is the precursor of several isoprenoid compounds including the farnesyl moiety of isoprenylated proteins. Inhibition of mevalonate biosynthesis leads to a growth arrest that can be relieved by addition of mevalonate, but not of cholesterol. To get a better understanding of the mechanisms underlying this growth inhibition, we have investigated whether mevalonate derivatives are implicated in the early response to growth factors. Our results show that pretreatment of quiescent human fibroblasts with mevinolin, an HMG CoA reductase inhibitor, partially suppresses fos and myc mRNA accumulation in response to serum stimulation. This effect of mevalonate deprivation appears to be on the transcriptional regulation of fos and does not depend upon the nature of the initial events of signal transduction, since the same phenomenon was observed following EGF and TPA stimulation.
Barbu
V
V
Laboratoire de Biochimie, CHU St Antoine, Paris, France.
Dautry
F
F
D015152:Blotting, Northern; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D066298:In Vitro Techniques; D008148:Lovastatin / Q000494:pharmacology; D008798:Mevalonic Acid / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D006133:Growth Substances; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D003609:Dactinomycin; D004815:Epidermal Growth Factor; D008148:Lovastatin; D013755:Tetradecanoylphorbol Acetate; D008798:Mevalonic Acid