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Int. J. Mol. Sci. 2017, 18(2), 304; doi:10.3390/ijms18020304

Jun Dimerization Protein 2 Activates Mc2r Transcriptional Activity: Role of Phosphorylation and SUMOylation

1
Department of Biomedical Sciences, Mercer University School of Medicine, Savannah, GA 31404, USA
2
Department of Genetics and Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA
*
Author to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 15 December 2016 / Revised: 16 January 2017 / Accepted: 26 January 2017 / Published: 31 January 2017
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

Jun dimerization protein 2 (JDP2), a basic leucine zipper transcription factor, is involved in numerous biological and cellular processes such as cancer development and regulation, cell-cycle regulation, skeletal muscle and osteoclast differentiation, progesterone receptor signaling, and antibacterial immunity. Though JDP2 is widely expressed in mammalian tissues, its function in gonads and adrenals (such as regulation of steroidogenesis and adrenal development) is largely unknown. Herein, we find that JDP2 mRNA and proteins are expressed in mouse adrenal gland tissues. Moreover, overexpression of JDP2 in Y1 mouse adrenocortical cancer cells increases the level of melanocortin 2 receptor (MC2R) protein. Notably, Mc2r promoter activity is activated by JDP2 in a dose-dependent manner. Next, by mapping the Mc2r promoter, we show that cAMP response elements (between −1320 and −720-bp) are mainly required for Mc2r activation by JDP2 and demonstrate that −830-bp is the major JDP2 binding site by real-time chromatin immunoprecipitation (ChIP) analysis. Mutations of cAMP response elements on Mc2r promoter disrupts JDP2 effect. Furthermore, we demonstrate that removal of phosphorylation of JDP2 results in attenuated transcriptional activity of Mc2r. Finally, we show that JDP2 is a candidate for SUMOylation and SUMOylation affects JDP2-mediated Mc2r transcriptional activity. Taken together, JDP2 acts as a novel transcriptional activator of the mouse Mc2r gene, suggesting that JDP2 may have physiological functions as a novel player in MC2R-mediated steroidogenesis as well as cell signaling in adrenal glands. View Full-Text
Keywords: Jun dimerization protein 2 (JDP2); melanocortin 2 receptor (MC2R); transcriptional activity; phosphorylation; SUMOylation Jun dimerization protein 2 (JDP2); melanocortin 2 receptor (MC2R); transcriptional activity; phosphorylation; SUMOylation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Wang, C.-M.; Wang, R.X.; Liu, R.; Yang, W.-H. Jun Dimerization Protein 2 Activates Mc2r Transcriptional Activity: Role of Phosphorylation and SUMOylation. Int. J. Mol. Sci. 2017, 18, 304.

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