1. An activator protein-1 complex mediates epidermal growth factor regulation of equine glycoprotein alpha subunit expression in trophoblast cells.
- Author
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Thway TM and Wolfe MW
- Subjects
- Animals, Base Sequence, Binding Sites, Choriocarcinoma, DNA chemistry, DNA metabolism, Humans, Mitogen-Activated Protein Kinases metabolism, Promoter Regions, Genetic, Protein Kinase C, Proto-Oncogene Proteins c-fos genetics, Proto-Oncogene Proteins c-jun genetics, Proto-Oncogene Proteins c-raf metabolism, Response Elements, Signal Transduction, Transcription Factor AP-1 pharmacology, Transfection, Tumor Cells, Cultured, Epidermal Growth Factor pharmacology, Gene Expression Regulation drug effects, Glycoprotein Hormones, alpha Subunit genetics, Horses genetics, Transcription Factor AP-1 metabolism, Trophoblasts metabolism
- Abstract
Equids and primates are the only species known to express the placental hormone chorionic gonadotropin (CG). CG is a member of the heterodimeric glycoprotein family and is composed of an alpha subunit linked to a hormone-specific beta subunit. Previously, we have reported that epidermal growth factor (EGF) regulates the equine glycoprotein hormone alpha subunit promoter through a protein kinase C (PKC)/mitogen-activated protein kinase (MAPK) signal transduction pathway in trophoblasts. The current study investigates the regulatory element/factors involved in the induction of equine glycoprotein alpha subunit gene expression by EGF. Using 5' deletion mutagenesis, we have delineated the primary EGF/PKC responsive region of the equine alpha subunit gene to be located between -2039 to -2032 base pairs upstream of the transcriptional start site. The sequence within this region contains an activator protein 1 (AP-1)-like response element (TGAATCA) and is similar to a consensus AP-1 (TGAC/GTCA) response element. This element appeared to preferentially interact with a c-fos/JunD heterodimer. Stimulation by EGF induced the binding of c-fos and JunD to this element and subsequently elevated promoter activity. In conclusion, an EGF/PKC/MAPK signal transduction pathway regulates equine glycoprotein alpha subunit gene expression through a distinct regulatory element(s) that lies between -2039 to -2032 of the equine glycoprotein alpha subunit promoter in trophoblasts and involves an AP-1 complex.
- Published
- 2002
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