The UPS and downs of cholesterol homeostasis.

Laura J Sharpe, Emma C L Cook, Noam Zelcer, Andrew J Brown

Journal: Trends in biochemical sciences 2015;39(11):527-35

PMID: 25220377

Full Text on Elsevier Science View on PubMed

Abstract

An emerging theme in the regulation of cholesterol homeostasis is the role of the ubiquitin proteasome system (UPS), through which proteins are ubiquitylated and then degraded in response to specific signals. The UPS controls all aspects of cholesterol metabolism including its synthesis, uptake, and efflux. We review here recent work uncovering the ubiquitylation and degradation of key players in cholesterol homeostasis. This includes the low-density lipoprotein (LDL) receptor, transcription factors (sterol regulatory element binding proteins and liver X receptors), flux-controlling enzymes in cholesterol synthesis (3-hydroxy-3-methylglutaryl-CoA reductase and squalene monooxygenase), and cholesterol exporters (ATP-binding cassette transporters ABCA1 and ABCG1). We explore which E3 ligases are involved, and identify areas deserving of further research.

Address: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW 2052, Australia.; Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105AZ Amsterdam, The Netherlands.; Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105AZ Amsterdam, The Netherlands. Electronic address: [email protected].; School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW 2052, Australia. Electronic address: [email protected].

DOI: 10.1016/j.tibs.2014.08.008

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MeSH Terms: ATP-Binding Cassette Transporters, Cholesterol, Homeostasis, Humans, Hydroxymethylglutaryl CoA Reductases, Models, Biological, Proteasome Endopeptidase Complex, Receptors, LDL, Squalene Monooxygenase, Transcription Factors, Ubiquitin, Ubiquitin-Protein Ligases