Journal
JOURNAL OF LIPID RESEARCH
Volume 55, Issue 3, Pages 410-420Publisher
ELSEVIER
DOI: 10.1194/jlr.M043257
Keywords
3 beta-hydroxysterol Delta 24-reductase; phosphorylation; bisindolylmaleimide I; protein kinase C; regulation; desmosterol; gas chromatography-mass spectrometry
Categories
Funding
- National Health and Medical Research Council [1008081]
- National Heart Foundation of Australia [G11S5757]
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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, 3 beta-hydroxysterol Delta 24-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.(jlr) Our data indicate a novel mechanism whereby DHCR24 activity is regulated by signaling.
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