期刊：
Biochemical and Biophysical Research Communications,2016年480(1):139-145 ISSN：0006-291X
通讯作者：
Chen, Jianxiong;Tuo, QH
作者机构：
[Xu, Guina; Sun, Shaowei; Wen, Juan; Xiong, Guozuo; Li, Tianping; Zhang, Caiping] Univ South China, Inst Pharm & Pharmacol, Sch Life Sci & Technol, Hengyang 421001, Hunan, Peoples R China.;[Nie, Juan; Tuo, Qinhui; Chen, Jianxiong; Chen, JX; Sun, Shaowei; Qiu, Fei; Liao, Duangfang] Hunan Univ Chinese Med, Sch Med, 300 Xueshi Rd, Changsha 410208, Hunan, Peoples R China.;[Yin, Yufang] Southern Illinois Univ, Dept Pharmacol, Sch Med, Springfield, IL 62702 USA.;[Chen, Jianxiong] Univ Mississippi, Med Ctr, Dept Pharmacol & Toxicol, Jackson, MS 39216 USA.
通讯机构：
[Chen, JX; Tuo, QH ] H;Hunan Univ Chinese Med, Sch Med, 300 Xueshi Rd, Changsha 410208, Hunan, Peoples R China.
关键词：
*Androgen receptor;*Cholesterol;*Fas death domain-associated protein;*SCAP;*SREBP
摘要：
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 SCAR. 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. (C) 2016 Elsevier Inc. All rights reserved.
