JDP2 Enhances Activation of the Mouse Mc2r Promoter

Presentation Number: MON-0388
Date of Presentation: June 23rd, 2014

Chiung-Min Wang1 and Wei-Hsiung Yang*2
1Mercer University School of Medicine, Savannah, GA, 2Mercer University School of Medi, Savannah, GA

Abstract

AP-1 is a heterodimeric protein and mainly consists of proteins belonging to c-Jun, c-Fos, activating transcription factor (ATF), and Jun dimerization protein (JDP) family. In addition to AP-1 site, JDP2 also binds to cAMP responsive element (CRE) site in numerous cis-elements of the target genes. In biological and cellular functions, JDP2 has been shown to be involved in cancer development and cell-cycle regulation, suppression of adipocyte differentiation, controlling replicative senescence, promoting skeletal muscle differentiation, mediating osteoclast differentiation, mediating atrial dilatation and atrial fibrillation, interacting with and regulating progesterone receptor, and controlling bone homeostasis and antibacterial immunity. Though JDP2 is widely expressed in mammalian tissues, its function in regulation of steroidogenesis and adrenal development is largely unknown. Herein, we first find that JDP2 is expressed in mouse adrenal gland tissues. Notably, Mc2r promoter activity is activated by JDP2 in a dose-dependent manner. Similarly, overexpression of JDP2 in Y1 mouse adrenocortical cancer cells increases the level of MC2R protein. By mapping the Mc2r promoter, we provide evidence that distal cAMP response elements (-1320 and -720) are mainly required for Mc2r activation by JDP2. Furthermore, we demonstrate that de-phosphorylation of JDP2 results in attenuated transcriptional activity of Mc2r. Taken together, we show for the time that JDP2 acts as a transcriptional activator of the mouse Mc2r gene. Our results suggest that JDP2 functions as a novel player in MC2R-mediated cell signaling as well as steroidogenesis in adrenal glands.

 

Nothing to Disclose: CMW, WHY