Transcriptional repression of the rat steroidogenic acute regulatory (StAR) protein gene by the AP-1 family member c-Fos.
PGF2alpha, working via protein kinase C, may inhibit transcription of the StAR gene through negative regulatory factors. Administration of PGF2alpha increased c-Fos mRNA with a corresponding reduction in StAR mRNA. A search of the rat StAR promoter revealed three putative AP-1 elements at bp positions -85, -187 and -1561, which demonstrated specific binding of c-Fos by mobility shift assays. Co-transfection of c-Fos with the p-1862 StAR promoter caused a reduction in luciferase activity in the presence or absence of cAMP. Mutation of all three AP-1 sites in the p-1862 StAR promoter abolished c-Fos repression. Mutation of the proximal AP-1 site in the p-1862 StAR promoter reduced SF-1 mediated induction. This study is the first to demonstrate that c-Fos represses StAR gene transcription and adds to the current knowledge on the complex relationship that exists between SF-1 and c-Fos in the regulation of StAR activity.
Shea-Eaton
Wendy
W
Departments of Obstetrics and Gynecology and Biochemistry and Molecular Biology, University of South Florida College of Medicine, 4 Columbia Drive, Rm 529, Tampa, FL 33606, USA.
Sandhoff
Todd W
TW
Lopez
Dayami
D
Hales
D Buck
DB
McLean
Mark P
MP
D000818:Animals; D015152:Blotting, Northern; D000242:Cyclic AMP / Q000494:pharmacology; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000378:metabolism; D015237:Dinoprost / Q000494:pharmacology*; D005260:Female; D051717:Fushi Tarazu Transcription Factors; D005786:Gene Expression Regulation / Q000502:physiology*; D018398:Homeodomain Proteins; D008156:Luciferases / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins / Q000378:metabolism*; D054339:Steroidogenic Factor 1; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D000098682:Steroidogenic Acute Regulatory Protein
D017931:DNA Primers; D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; D010750:Phosphoproteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; D054339:Steroidogenic Factor 1; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D000098682:Steroidogenic Acute Regulatory Protein; D015237:Dinoprost; D000242:Cyclic AMP; D008156:Luciferases