期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 480, 期 1, 页码 139-145出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2016.09.102
关键词
Fas death domain-associated protein; Androgen receptor; SCAP; SREBP; Cholesterol
资金
- National Natural Science Foundation of China [30971267, 81673722, 81670268, 81600291]
- Natural Science Foundation of Hunan Province [2016JJ3109, 2015JJ2117]
- Key projects of Hunan Provincial Department of Education [16A156]
- Hunan Province National Funds for Distinguished Young Scientists [14JJ1024]
- One Hundred Talent Program of Human Province
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.
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