Signaling regulates activity of DHCR24, the final enzyme in cholesterol synthesis.

Journal of Lipid Research
Winnie LuuAndrew J Brown

Abstract

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.

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Citations

Sep 16, 2014·Trends in Biochemical Sciences·Laura J SharpeAndrew J Brown
Nov 5, 2016·Progress in Lipid Research·Anika V PrabhuAndrew J Brown
Dec 19, 2016·Journal of the American College of Cardiology·Annapoorna S KiniSamin Sharma
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Apr 4, 2019·The Journal of Biological Chemistry·Ngee Kiat ChuaAndrew J Brown
May 8, 2020·BMC Cardiovascular Disorders·Zikai SongShuping Ren
Dec 6, 2017·International Journal of Molecular Medicine·Yeseung LeeYoungja H Park
Oct 15, 2020·The Journal of Biological Chemistry·Laura J SharpeAndrew J Brown
Jan 18, 2021·The Journal of Biological Chemistry·Laura J SharpeAndrew J Brown
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May 29, 2021·Environmental Science and Pollution Research International·Guangzhu DongGuizhen Du
May 20, 2021·Biochemical Pharmacology·Babita MadanDavid J Leaver
Sep 11, 2021·Frontiers in Cell and Developmental Biology·Lin XiongXian Guo

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