An activator protein-1 complex mediates epidermal growth factor regulation of equine glycoprotein alpha subunit expression in trophoblast cells.

This study examines how the Epidermal Growth Factor (EGF) affects the expression of the alpha subunit of glycoprotein hormone in horse’s trophoblast cells by targeting a specific protein complex called Activator Protein-1 (AP-1).

Study Focus and Background

• The research is focused on the regulation of the equine glycoprotein hormone alpha subunit gene expression by EGF. This gene expression holds significance as only primates and equids (horses) express the placental hormone known as chorionic gonadotropin (CG).
• CG is a hormone-specific beta subunit linked to an alpha subunit, and belongs to the heterodimeric glycoprotein family. Expression of this hormone’s alpha subunit comes under the influence of EGF, which was earlier noted by researchers. The precise mechanism of this influence operates via the protein kinase C (PKC)/mitogen-activated protein kinase (MAPK) signal transduction pathway in trophoblasts cells.

Investigating the Regulatory Factors

• In this study, the researchers aimed to further explore the specific regulatory elements or factors that facilitate the effect of EGF on the alpha subunit gene expression. The researchers achieved this aim using a 5′ deletion mutagenesis method.
• The EGF/PKC responsive region of the equine alpha subunit gene was identified to be located between the -2039 to -2032 base pairs, upstream of the transcriptional start site. This region carried a sequence resembling a response element to activator protein 1 (AP-1).
• The sequence contained an AP-1-like response element (TGAATCA) similar to that of a consensus AP-1 (TGAC/GTCA) response element, which interacted preferentially with a c-fos/JunD heterodimer.

EGF’s Role in Gene Expression

• Upon stimulation by EGF, it was observed that the binding of c-fos and JunD to this element was induced, causing an increase in promoter activity.
• Conclusively, the EGF/PKC/MAPK signal transduction pathway showed responsibility for the regulation of the glycoprotein alpha subunit gene expression in equine trophoblasts. This activity utilizes a specific regulatory element lying between the -2039 and -2032 base pairs of the gene’s promoter that involves the AP-1 protein complex.