HMG CoA Reductase and lnsig-1: Regulatory Roles of ERAD

Debose-Boyd, Russell Alfred

Abstract

HMG CoA reductase is the molecular target of statins, a group of drugs that are widely prescribed to lower plasma LDL-cholesterol and to reduce the incidence of cardiovascular disease in humans. Statins trigger regulatory responses that result in the marked accumulation of reductase that blunts the clinical effects of the drugs. Part of this increase is likely due to slowed ERAD of reductase. Thus, understanding the mechanisms of reductase ERAD may lead to the development of new drugs to counteract the accumulation of reductase that accompanies statin treatment. In some cases these drugs may provide alternatives to statin therapy.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Heart, Lung, and Blood Institute (NHLBI)
• Type: Research Program Projects (P01)
• Project #: 5P01HL020948-38
• Application #: 8686023
• Study Section: Heart, Lung, and Blood Program Project Review Committee (HLBP)
• Budget Start: 2014-07-01
• Budget End: 2015-06-30
• Support Year: 38
• Fiscal Year: 2014

Institution

• Name: University of Texas Sw Medical Center Dallas
• City: Dallas
• State: TX
• Country: United States
• Zip Code: 75390

Publications

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Schumacher, Marc M; Jun, Dong-Jae; Johnson, Brittany M et al. (2018) UbiA prenyltransferase domain-containing protein-1 modulates HMG-CoA reductase degradation to coordinate synthesis of sterol and nonsterol isoprenoids. J Biol Chem 293:312-323

Mitsche, Matthew A; Hobbs, Helen H; Cohen, Jonathan C (2018) Patatin-like phospholipase domain-containing protein 3 promotes transfer of essential fatty acids from triglycerides to phospholipids in hepatic lipid droplets. J Biol Chem 293:6958-6968

Banfi, Serena; Gusarova, Viktoria; Gromada, Jesper et al. (2018) Increased thermogenesis by a noncanonical pathway in ANGPTL3/8-deficient mice. Proc Natl Acad Sci U S A 115:E1249-E1258

Fine, Michael; Schmiege, Philip; Li, Xiaochun (2018) Structural basis for PtdInsP2-mediated human TRPML1 regulation. Nat Commun 9:4192

Linden, Albert G; Li, Shili; Choi, Hwa Y et al. (2018) Interplay between ChREBP and SREBP-1c coordinates postprandial glycolysis and lipogenesis in livers of mice. J Lipid Res 59:475-487

Johnson, Brittany M; DeBose-Boyd, Russell A (2018) Underlying mechanisms for sterol-induced ubiquitination and ER-associated degradation of HMG CoA reductase. Semin Cell Dev Biol 81:121-128

Qi, Xiaofeng; Schmiege, Philip; Coutavas, Elias et al. (2018) Two Patched molecules engage distinct sites on Hedgehog yielding a signaling-competent complex. Science 362:

Engelking, Luke J; Cantoria, Mary Jo; Xu, Yanchao et al. (2018) Developmental and extrahepatic physiological functions of SREBP pathway genes in mice. Semin Cell Dev Biol 81:98-109

Hobbs, Helen H (2018) Science, serendipity, and the single degree. J Clin Invest 128:4218-4223