Phosphorylation regulates activity of 7-dehydrocholesterol reductase (DHCR7), a terminal enzyme of cholesterol synthesis

Autor: Laura J. Sharpe, Andrew J. Brown, Winnie Luu, Anika V. Prabhu
Rok vydání: 2017
Předmět:
0301 basic medicine
Oxidoreductases Acting on CH-CH Group Donors
congenital
hereditary
and neonatal diseases and abnormalities
7-Dehydrocholesterol reductase
Endocrinology
Diabetes and Metabolism
Clinical Biochemistry
CHO Cells
AMP-Activated Protein Kinases
Reductase
Biology
Cholesterol 7 alpha-hydroxylase
Biochemistry
Gas Chromatography-Mass Spectrometry
Gene Expression Regulation
Enzymologic
03 medical and health sciences
Cricetulus
0302 clinical medicine
Endocrinology
Cricetinae
Ca2+/calmodulin-dependent protein kinase
Animals
Humans
Phosphorylation
RNA
Small Interfering
Vitamin D
Protein kinase A
Molecular Biology
Kinase
Cell Biology
Cyclic AMP-Dependent Protein Kinases
Smith-Lemli-Opitz Syndrome
Cholesterol
030104 developmental biology
030220 oncology & carcinogenesis
Mutation
HMG-CoA reductase
Mutagenesis
Site-Directed
biology.protein
Molecular Medicine
lipids (amino acids
peptides
and proteins)
Zdroj: The Journal of Steroid Biochemistry and Molecular Biology. 165:363-368
ISSN: 0960-0760
Popis: Cholesterol is essential for survival, but too much or too little can cause disease. Thus, cholesterol levels must be kept within close margins. 7-dehydrocholesterol reductase (DHCR7) is a terminal enzyme of cholesterol synthesis, and is essential for embryonic development. Largely, DHCR7 research is associated with the developmental disease Smith-Lemli-Opitz syndrome, which is caused by mutations in the DHCR7 gene. However, little is known about what regulates DHCR7 activity. Here we provide evidence that phosphorylation plays a role in controlling DHCR7 activity, which may provide a means to divert flux from cholesterol synthesis to vitamin D production. DHCR7 activity was significantly decreased when we used pharmacological inhibitors against two important kinases, AMP-activated protein kinase and protein kinase A. Moreover, mutating a known phosphorylated residue, S14, also decreased DHCR7 activity. Thus, we demonstrate that phosphorylation modulates DHCR7 activity in cells, and contributes to the overall synthesis of cholesterol, and probably vitamin D.
Databáze: OpenAIRE
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