Insulin-like growth factor-I stimulates c-fos and c-jun transcription in PC12 cells.
We analyzed the effects of insulin-like growth factor-I (IGF-I), a polypeptide growth factor which exerts mitogenic effects via specific membrane receptors. The control of IGF-I on c-fos and c-jun transcription was studied in PC12 cells. Gel mobility shift assays with a labeled AP1 consensus binding sequence (TRE: TGACTCA) showed an increase in specific binding upon trIGF-treatment. Gene transfer studies revealed that the increase in AP1 binding is functional since IGF-I stimulates transcription from a reporter gene containing the minimal TRE linked to the chloramphenicol acetyl transferase (CAT) reporter gene. To further characterize the molecular mechanism by which IGF-I increases AP1 activity, we analysed the transcription regulation of c-fos and c-jun using reporter genes containing the respective promoters or specific regulatory elements. Deletion studies with the c-jun promoter, showed that IGF-I stimulates c-jun transcription via a cis acting element(s) localized within the 132 base pairs prior to the transcription start site; possibly the AP1 like element TGACATCA. Similar studies revealed that c-fos stimulation by IGF-I requires the presence of a regulatory sequence spanning the dyad symmetry element (DSE) and the fos AP1-like sequence (FAP). Further experiments using specific elements linked to the minimal unresponsive c-fos promoter, showed that the DSE is the main target for c-fos induction by IGF-I.
Monnier
D
D
Institut de Physiologie et de Chimie Biologique, URA 1446 CNRS, Strasbourg, France.
Boutillier
A L
AL
Giraud
P
P
Chiu
R
R
Aunis
D
D
Feltz
P
P
Zwiller
J
J
Loeffler
J P
JP
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D016384:Consensus Sequence; D017353:Gene Deletion; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D016762:Genes, fos / Q000235:genetics*; D016758:Genes, jun / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008969:Molecular Sequence Data; D016716:PC12 Cells / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic
D018808:Transcription Factor AP-1; D007334:Insulin-Like Growth Factor I; D015500:Chloramphenicol O-Acetyltransferase; D013755:Tetradecanoylphorbol Acetate