文章基本信息

标题：Signaling regulates activity of DHCR24, the final enzyme in cholesterol synthesis
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作者：Winnie Luu ; Eser J. Zerenturk ; Ika Kristiana 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2014
卷号：55
期号：3
页码：410-420
DOI：10.1194/jlr.M043257
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：The role of signaling in regulating cholesterol homeostasis is gradually becoming more widely recognized. Here, we explored how kinases and phosphorylation sites regulate the activity of the enzyme involved in the final step of cholesterol synthesis, 3β-hydroxysterol Δ24-reductase (DHCR24). Many factors are known to regulate DHCR24 transcriptionally, but little is known about its posttranslational regulation. We developed a system to specifically test human ectopic DHCR24 activity in a model cell-line (Chinese hamster ovary-7) using siRNA targeted only to hamster DHCR24, thus ensuring that all activity could be attributed to the human enzyme. We determined the effect of known phosphorylation sites and found that mutating certain residues (T110, Y299, and Y507) inhibited DHCR24 activity. In addition, inhibitors of protein kinase C ablated DHCR24 activity, although not through a known phosphorylation site. Our data indicate a novel mechanism whereby DHCR24 activity is regulated by signaling.
关键词：3β-hydroxysterol Δ24-reductase ; phosphorylation ; bisindolylmaleimide I ; protein kinase C ; regulation ; desmosterol ; gas chromatography-mass spectrometry