Haploid Mammalian Genetic Screen Identifies UBXD8 as a Key Determinant of HMGCR Degradation and Cholesterol Biosynthesis

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 37; no. 11; pp. 2064 - 2074
• Main Authors: Loregger, Anke, Raaben, Matthijs, Tan, Josephine, Scheij, Saskia, Moeton, Martina, van den Berg, Marlene, Gelberg-Etel, Hila, Stickel, Elmer, Roitelman, Joseph, Brummelkamp, Thijn, Zelcer, Noam
• Format: Journal Article
• Language: English
• Published: United States American Heart Association, Inc 01.11.2017; Lippincott Williams & Wilkins
• Subjects: Animals; Basic Sciences; Blood Proteins - genetics; Blood Proteins - metabolism; Cholesterol - biosynthesis; CRISPR-Cas Systems; Endoplasmic Reticulum - enzymology; Enzyme Stability; Feedback, Physiological; Gene Expression Regulation, Enzymologic; Haploidy; Hep G2 Cells; Hepatocytes - enzymology; Humans; Hydroxymethylglutaryl CoA Reductases - genetics; Hydroxymethylglutaryl CoA Reductases - metabolism; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mevalonic Acid - metabolism; Microscopy, Confocal; Proteasome Endopeptidase Complex - metabolism; Protein Transport; Proteolysis; Rats; Recombinant Fusion Proteins - metabolism; Transfection; Ubiquitination; cholesterol; sterols; hydroxymethylglutaryl CoA reductases; mammalian haploid genetics; oxysterols
• ISSN: 1079-5642; 1524-4636; 1524-4636
• DOI: 10.1161/ATVBAHA.117.310002

OBJECTIVE—The cellular demand for cholesterol requires control of its biosynthesis by the mevalonate pathway. Regulation of HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase), a rate-limiting enzyme in this pathway and the target of statins, is a key control point herein. Accordingly, HMGCR is...