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Stimulus-Induced Activation of the Glycoprotein Hormone α-Subunit Promoter in Human Placental Choriocarcinoma Cells: Major role of a Tandem cAMP Response Element
Bürvenich, L.; Rössler, O.G.; Thiel, G. Stimulus-Induced Activation of the Glycoprotein Hormone α-Subunit Promoter in Human Placental Choriocarcinoma Cells: Major Role of a Tandem CAMP Response Element. Current Issues in Molecular Biology 2024, 46, 3218–3235, doi:10.3390/cimb46040202.
Bürvenich, L.; Rössler, O.G.; Thiel, G. Stimulus-Induced Activation of the Glycoprotein Hormone α-Subunit Promoter in Human Placental Choriocarcinoma Cells: Major Role of a Tandem CAMP Response Element. Current Issues in Molecular Biology 2024, 46, 3218–3235, doi:10.3390/cimb46040202.
Bürvenich, L.; Rössler, O.G.; Thiel, G. Stimulus-Induced Activation of the Glycoprotein Hormone α-Subunit Promoter in Human Placental Choriocarcinoma Cells: Major Role of a Tandem CAMP Response Element. Current Issues in Molecular Biology 2024, 46, 3218–3235, doi:10.3390/cimb46040202.
Bürvenich, L.; Rössler, O.G.; Thiel, G. Stimulus-Induced Activation of the Glycoprotein Hormone α-Subunit Promoter in Human Placental Choriocarcinoma Cells: Major Role of a Tandem CAMP Response Element. Current Issues in Molecular Biology 2024, 46, 3218–3235, doi:10.3390/cimb46040202.
Abstract
The glycoprotein hormones luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone and chorionic gonadotropin consist of a common alpha-subunit and a hormone-specific beta-subunit. The alpha-subunit is expressed in thyrotrophs, gonadotrophs, and placental cells, and its expression is regulated by extracellular signal molecules. Here, we assessed the regulation of the gene encoding the alpha-subunit in placental JEG-3 cells, using a chromatin-embedded reporter gene under the control of the glycoprotein hormone alpha-subunit promoter. The results show that stimulation of the cells with forskolin, an activator of adenylate cyclase, induced transcription of a reporter gene controlled by the alpha-subunit promoter. Similarly, expression of a nuclear-targeted catalytic subunit of cAMP-dependent protein kinase increased reporter gene transcription. Expression experiments involving constitutively active mutants of MKK6 and MEKK-1 showed that the alpha-subunit promoter is responsive to activation of p38 protein kinase but only slightly responsive to activation of c-Jun N-terminal protein kinase. Finally, we show that stimulation of a Galphaq-coupled designer receptor triggers transcription of a reporter gene controlled by the glycoprotein hormone alpha-subunit promoter, mediated by the transcription factor CREB. Deletion mutagenesis highlights the importance of a tandem cAMP response element within the alpha-subunit promoter that acts as a point of convergence for different signaling pathways.
Biology and Life Sciences, Biochemistry and Molecular Biology
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