A wolf in sheep's clothing: unmasking the lanosterol-induced degradation of HMG-CoA reductase

doi:10.1194/jlr.C119000358

Comment

. 2019 Oct;60(10):1643-1645.

doi: 10.1194/jlr.C119000358. Epub 2019 Aug 28.

A wolf in sheep's clothing: unmasking the lanosterol-induced degradation of HMG-CoA reductase

Hudson W Coates¹, Andrew J Brown²

Affiliations

¹ School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia.
² School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia aj.brown@unsw.edu.au.

PMID: 31462514
PMCID: PMC6795080
DOI: 10.1194/jlr.C119000358

Comment

A wolf in sheep's clothing: unmasking the lanosterol-induced degradation of HMG-CoA reductase

Hudson W Coates et al. J Lipid Res. 2019 Oct.

. 2019 Oct;60(10):1643-1645.

doi: 10.1194/jlr.C119000358. Epub 2019 Aug 28.

Authors

Hudson W Coates¹, Andrew J Brown²

Affiliations

¹ School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia.
² School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia aj.brown@unsw.edu.au.

PMID: 31462514
PMCID: PMC6795080
DOI: 10.1194/jlr.C119000358

No abstract available

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Figures

**Fig. 1.**
Mevalonate pathway intermediates active in feedback control. Accumulation of C4-dimethylated intermediates of the Bloch and Kandutsch-Russell pathways (gray box) accelerates the degradation of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR; solid red line) and, with the exception of lanosterol, the inactivation of sterol response element binding protein-2 (SREBP-2; dashed red line). C4-dimethyl moieties and C24-saturated bonds of sterol molecules are indicated in blue and orange, respectively. Enzymes knocked out in the study by Chen et al. are indicated in green. Dashed arrows indicate multiple enzymatic steps.

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Comment on

Endogenous sterol intermediates of the mevalonate pathway regulate HMGCR degradation and SREBP-2 processing.
Chen L, Ma MY, Sun M, Jiang LY, Zhao XT, Fang XX, Man Lam S, Shui GH, Luo J, Shi XJ, Song BL. Chen L, et al. J Lipid Res. 2019 Oct;60(10):1765-1775. doi: 10.1194/jlr.RA119000201. Epub 2019 Aug 27. J Lipid Res. 2019. PMID: 31455613 Free PMC article.

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References

1. Goldstein J. L., and Brown M. S.. 1990. Regulation of the mevalonate pathway. Nature. 343: 425–430. - PubMed
1. Brown M. S., Radhakrishnan A., and Goldstein J. L.. 2018. Retrospective on cholesterol homeostasis: the central role of Scap. Annu. Rev. Biochem. 87: 783–807. - PMC - PubMed
1. Kandutsch A. A., Chen H. W., and Heiniger H. J.. 1978. Biological activity of some oxygenated sterols. Science. 201: 498–501. - PubMed
1. Sharpe L. J., and Brown A. J.. 2013. Controlling cholesterol synthesis beyond 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). J. Biol. Chem. 288: 18707–18715. - PMC - PubMed
1. Radhakrishnan A., Ikeda Y., Kwon H. J., Brown M. S., and Goldstein J. L.. 2007. Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: Oxysterols block transport by binding to Insig. Proc. Natl. Acad. Sci. USA. 104: 6511–6518. - PMC - PubMed

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[1] Goldstein J. L., and Brown M. S.. 1990. Regulation of the mevalonate pathway. Nature. 343: 425–430. - PubMed

[2] Goldstein J. L., and Brown M. S.. 1990. Regulation of the mevalonate pathway. Nature. 343: 425–430. - PubMed

[3] Brown M. S., Radhakrishnan A., and Goldstein J. L.. 2018. Retrospective on cholesterol homeostasis: the central role of Scap. Annu. Rev. Biochem. 87: 783–807. - PMC - PubMed

[4] Brown M. S., Radhakrishnan A., and Goldstein J. L.. 2018. Retrospective on cholesterol homeostasis: the central role of Scap. Annu. Rev. Biochem. 87: 783–807. - PMC - PubMed

[5] Kandutsch A. A., Chen H. W., and Heiniger H. J.. 1978. Biological activity of some oxygenated sterols. Science. 201: 498–501. - PubMed

[6] Kandutsch A. A., Chen H. W., and Heiniger H. J.. 1978. Biological activity of some oxygenated sterols. Science. 201: 498–501. - PubMed

[7] Sharpe L. J., and Brown A. J.. 2013. Controlling cholesterol synthesis beyond 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). J. Biol. Chem. 288: 18707–18715. - PMC - PubMed

[8] Sharpe L. J., and Brown A. J.. 2013. Controlling cholesterol synthesis beyond 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). J. Biol. Chem. 288: 18707–18715. - PMC - PubMed

[9] Radhakrishnan A., Ikeda Y., Kwon H. J., Brown M. S., and Goldstein J. L.. 2007. Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: Oxysterols block transport by binding to Insig. Proc. Natl. Acad. Sci. USA. 104: 6511–6518. - PMC - PubMed

[10] Radhakrishnan A., Ikeda Y., Kwon H. J., Brown M. S., and Goldstein J. L.. 2007. Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: Oxysterols block transport by binding to Insig. Proc. Natl. Acad. Sci. USA. 104: 6511–6518. - PMC - PubMed

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A wolf in sheep's clothing: unmasking the lanosterol-induced degradation of HMG-CoA reductase

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A wolf in sheep's clothing: unmasking the lanosterol-induced degradation of HMG-CoA reductase

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