Identification of the C-terminal domain of Daxx acts as a potential regulator of intracellular cholesterol synthesis in HepG2 cells.

Identification of the C-terminal domain of Daxx acts as a potential regulator of intracellular cholesterol synthesis in HepG2 cells.
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Daxx C 末端结构域的鉴定作为 HepG2 细胞内胆固醇合成的潜在调节剂

DOI:
10.1016/j.bbrc.2016.09.102
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发表时间:
2016-11
期刊:
Biochem Biophys Res Commun
影响因子:
--
通讯作者:
Tuo Qinhui
Tuo Qinhui
中科院分区:
其他
文献类型:
--
作者:
Sun Shaowei;Wen Juan;Qiu Fei;Yin Yufang;Xu Guina;Li Tianping;Nie Juan;Xiong Guozuo;Zhang Caiping;Liao Duangfang;Chen Jianxiong;Tuo Qinhui

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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.
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