Identification of the C-terminal domain of Daxx acts as a potential regulator of intracellular cholesterol synthesis in HepG2 cells.
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.
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.
Shaowei
S
Sun
Institute of Pharmacy and Pharmacology, School of Life Science and Technology, University of South China, Hengyang 421001, Hunan, China.
Juan
J
Wen
Medical School, Hunan University of Chinese Medicine, Changsha 410208, Hunan, China.
Fei
F
Qiu
Department of Pharmacology, Medical School of Southern Illinois University, Springfield, IL 62702, USA.
Yufang
Y
Yin
Institute of Pharmacy and Pharmacology, School of Life Science and Technology, University of South China, Hengyang 421001, Hunan, China.
Guina
G
Xu
Institute of Pharmacy and Pharmacology, School of Life Science and Technology, University of South China, Hengyang 421001, Hunan, China.
Tianping
T
Li
Medical School, Hunan University of Chinese Medicine, Changsha 410208, Hunan, China.
Juan
J
Nie
Institute of Pharmacy and Pharmacology, School of Life Science and Technology, University of South China, Hengyang 421001, Hunan, China.
Guozuo
G
Xiong
Institute of Pharmacy and Pharmacology, School of Life Science and Technology, University of South China, Hengyang 421001, Hunan, China.
Caiping
C
Zhang
Medical School, Hunan University of Chinese Medicine, Changsha 410208, Hunan, China.
Duangfang
D
Liao
Medical School, Hunan University of Chinese Medicine, Changsha 410208, Hunan, China; Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, USA. Electronic address: JChen3@umc.edu.
Jianxiong
J
Chen
Medical School, Hunan University of Chinese Medicine, Changsha 410208, Hunan, China. Electronic address: qhtuo@aliyun.com.
Qinhui
Q
Tuo
D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002784:Cholesterol / Q000096:biosynthesis*; D056970:Co-Repressor Proteins; D056945:Hep G2 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000072417:Protein Domains; D011944:Receptors, Androgen / Q000378:metabolism; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics / Q000378:metabolism
C410798:AR protein, human; D048868:Adaptor Proteins, Signal Transducing; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D011944:Receptors, Androgen; C497390:SREBF2 protein, human; C102196:SREBP cleavage-activating protein; D051782:Sterol Regulatory Element Binding Protein 2; D002784:Cholesterol
Androgen receptor; Cholesterol; Fas death domain-associated protein; SCAP; SREBP