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An activator protein-1 complex mediates epidermal growth factor regulation of equine glycoprotein alpha subunit expression in trophoblast cells.
- Source :
-
Biology of reproduction [Biol Reprod] 2002 Sep; Vol. 67 (3), pp. 972-80. - Publication Year :
- 2002
-
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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 0006-3363
- Volume :
- 67
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Biology of reproduction
- Publication Type :
- Academic Journal
- Accession number :
- 12193410
- Full Text :
- https://doi.org/10.1095/biolreprod.101.001057