Essential role of the homeodomain for pituitary homeobox 1 activation of mouse gonadotropin-releasing hormone receptor gene expression through interactions with c-Jun and DNA

Molecular and Cellular Biology
Kyeong-Hoon JeongU B Kaiser

Abstract

The gonadotropin-releasing hormone receptor (GnRHR) is expressed primarily in the gonadotropes of the anterior pituitary. Pituitary homeobox 1 (Pitx-1) has been shown to activate pituitary-specific gene expression by direct DNA binding and/or protein-protein interaction with other transcription factors. We hypothesized that Pitx-1 might also dictate tissue-specific expression of the mouse GnRHR (mGnRHR) gene in a similar manner. Pitx-1 activated the mGnRHR gene promoter, and transactivation was localized to sequences between -308 and -264. Pitx-1 bound to this region only with low affinity. This region includes an activating protein 1 (AP-1) site, which was previously shown to be important for mGnRHR gene expression. Further characterization indicated that an intact AP-1 site was required for full Pitx-1 responsiveness. Furthermore, Pitx-1 and AP-1 were synergistic in the activation of the mGnRHR gene promoter. A Pitx-1 homeodomain (HD) point mutation, which eliminated DNA binding ability, caused only a partial reduction of transactivation, whereas deletion of the HD completely prevented transactivation. Pitx-1 interacted directly with c-Jun, and the HD was sufficient for this interaction. While the point mutation in the Pitx-1...Continue Reading

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Citations

Feb 12, 2005·Endocrinology·Shauna M McGillivrayPamela L Mellon
Sep 27, 2014·Journal of Molecular Endocrinology·Alina GajewskaLech Zwierzchowski
Mar 24, 2011·Leukemia & Lymphoma·Stefan NagelRoderick A F Macleod
Aug 28, 2010·Molecular and Cellular Endocrinology·Weiming ZhengLisa M Halvorson
Nov 21, 2007·Molecular and Cellular Endocrinology·Magdalena I SuszkoTeresa K Woodruff
Sep 15, 2005·Journal of Neuroendocrinology·J P HapgoodK Ronacher
May 6, 2015·Molecular Endocrinology·Jérôme FortinDaniel J Bernard
Jan 11, 2008·The Journal of Biological Chemistry·Amy L BlountLouise M Bilezikjian

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