Sun Shaowei, Wen Juan, Qiu Fei, Yin Yufang, Xu Guina, Li Tianping, Nie Juan, Xiong Guozuo, Zhang Caiping, Liao Duangfang, Chen Jianxiong, Tuo Qinhui
Institute of Pharmacy and Pharmacology, School of Life Science and Technology, University of South China, Hengyang 421001, Hunan, China; Medical School, Hunan University of Chinese Medicine, Changsha 410208, Hunan, China.
Institute of Pharmacy and Pharmacology, School of Life Science and Technology, University of South China, Hengyang 421001, Hunan, China.
Biochem Biophys Res Commun. 2016 Nov 4;480(1):139-145. doi: 10.1016/j.bbrc.2016.09.102. Epub 2016 Sep 23.
Daxx is a highly conserved nuclear transcriptional factor, which has been implicated in many nuclear processes including transcription and cell cycle regulation. Our previous study demonstrated Daxx also plays a role in regulation of intracellular cholesterol content. Daxx contains several domains that are essential for interaction with a growing number of proteins. To delineate the underlying mechanism of hypocholesterolemic activity of Daxx, we constructed a set of plasmids which can be used to overexpress different fragments of Daxx and transfected to HepG2 cells. We found that the C- terminal region Daxx626-740 clearly reduced intracellular cholesterol levels and inhibited the expression of SREBPs and SCAP. In GST pull-down experiments and Double immunofluorescence assays, Daxx626-740 was demonstrated to bind directly to androgen receptor (AR). Our findings suggest that the interaction of Daxx626-740 and AR abolishes the AR-mediated activation of SCAP/SREBPs pathway, which suppresses the de novo cholesterol synthesis. Thus, C-terminal domain of Daxx acts as a potential regulator of intracellular cholesterol content in HepG2 cells.
