Rapid downregulation of transcription mediated by the cAMP response element of c-fos promoter does not require new protein synthesis.
Induction of the c-fos gene is well known to be transient, due to autorepression of its transcription. While the dyad symmetry element (DSE) in the c-fos promoter has been shown to mediate transient c-fos transcription in response to serum, it is yet unknown whether the cAMP response elements (CREs) in the promoter mediate transient transcription in response to cAMP. We observed that forskolin induced transient expression of the c-fos gene in the presence of a calcium ionophore A23187 in NIH3T3 fibroblasts. We investigated transcriptional abilities of one of the CREs (-60 CRE) as well as the DSE. Both of the elements mediated the synergistic effects of forskolin and A23187 on transcription. Transcription driven by the -60 CRE was downregulated at around 2 hrs. after stimulation of forskolin plus A23187 with similar kinetics to that by the DSE. The downregulation with the -60 CRE was less sensitive to an inhibitor of protein synthesis comparing with that by the DSE. These results suggest that function of the -60 CRE activated by forskolin plus A23187 is downregulated by activation of pre-existing factors.
Kikuchi
K
K
Department of Chemical Engineering, Faculty of Engineering, University of Tokyo, Japan.
Makishima
F
F
Nishimura
H
H
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D000001:Calcimycin / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics*; D016762:Genes, fos / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D013449:Sulfonamides / Q000494:pharmacology
D002147:Calmodulin; D013449:Sulfonamides; D005576:Colforsin; D000001:Calcimycin; C017967:W 7; D000242:Cyclic AMP