Signaling Regulates Activity of DHCR24, the Final Enzyme in Cholesterol Synthesis
MetadataShow full item record
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.
Showing items related by title, author, creator and subject.
Luu, W.; Zerenturk, E.; Kristiana, Ina; Bucknal, M.; Sharpe, L.; Brown, A. (2014)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 ...
Induction of apoptosis in murine malignant mesothelioma cell lines: gene expression and susceptibilityKusmiaty (2003)Malignant mesothelioma (MM) is an aggressive and highly chemo-resistant tumour of the mesothelium. Asbestos is indicated as the environmental factor most commonly associated with mesothelioma. The chemo-resistance is ...
Diminished Ost3-dependent N-glycosylation of the BiP nucleotide exchange factor Sil1 is an adaptive response to reductive ER stressStevens, K.; Black, A.; Wells, K.; Yeo, K.; Steuart, R.; Stirling, C.; Schulz, B.; Mousley, Carl (2017)© 2017, National Academy of Sciences. All rights reserved. BiP (Kar2 in yeast) is an essential Hsp70 chaperone and master regulator of endoplasmic reticulum (ER) function. BiP’s activity is regulated by its intrinsic ...