Expression of the transcriptional repressor ATF3 in gonadotrophs is regulated by Egr-1, CREB, and ATF2 after gonadotropin-releasing hormone receptor stimulation

Endocrinology
Sabine I MayerGerald Thiel

Abstract

Stimulation of GnRH receptors enhances expression of activating transcription factor (ATF) 3 in a pituitary gonadotroph cell line. The signaling pathway requires elevated cytosolic Ca2+ levels and activation of ERK and c-Jun N-terminal protein kinase. The signaling cascade was blocked by overexpression of either MAPK phosphatase (MKP)-1 or MAPK phosphatase-5 that dephosphorylate nuclear ERK and c-Jun N-terminal protein kinase. In addition, ATF3 biosynthesis was impaired after lentiviral-mediated expression of a constitutively active mutant of calcineurin A. Thus, MKP-1, MKP-5, and calcineurin may function as shut-off devices for GnRH receptor signaling. Expression of dominant-negative mutants of early growth response protein (Egr)-1, cAMP response element binding protein (CREB), and ATF2 blocked the biosynthesis of ATF3, indicating that these transcription factors connect the intracellular signaling cascade elicited by activation of GnRH receptors with transcription of the ATF3 gene. This view was corroborated by chromatin immunoprecipitation experiments revealing that Egr-1 and the phosphorylated forms of CREB and ATF2 bound to the 5'-upstream region of the ATF3 gene in buserelin-stimulated gonadotrophs. Together the data indi...Continue Reading

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Citations

Jun 12, 2013·Integrative Biology : Quantitative Biosciences From Nano to Macro·Ana M C BarradasJan de Boer
Jun 30, 2011·The Journal of Biological Chemistry·Nolan G GokeyJohn Svaren
Mar 27, 2012·Molecular Endocrinology·April K BinderJohn H Nilson
Mar 19, 2014·Molecular and Cellular Endocrinology·Gerald ThielOliver G Rössler
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Sep 15, 2011·Endocrinology·Gerald Thiel, Oliver G Rössler
Aug 21, 2012·Endocrinology·Gerald ThielAnja Keim
Jun 10, 2016·Journal of Cellular Biochemistry·Oliver G Rössler, Gerald Thiel
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Jul 25, 2021·Biochemical Pharmacology·Gerald ThielOliver G Rössler
Aug 31, 2021·Biochemical Pharmacology·Tobias M BackesGerald Thiel

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