Cell membranes are fundamental to life, and defects in their function underlie many diseases. Membranes of different organelles have different lipid compositions. For example, cholesterol is markedly enriched in the plasma membrane compared with the ER. Scientists know the enzymes that synthesize and degrade the various lipids in different cell membranes. Yet, very little is known about how these enzymes are regulated so as to maintain differential lipid compositions. Our laboratory made the initial inroad into this problem through the discovery of the SREBP family of transcription factors that control synthesis and uptake of cholesterol and fatty acids. We discovered four proteins whose actions govern the regulated trafficking mechanism that dictates the activities of SREBPs. We are now in a unique position to decipher precisely how this system works at a molecular level.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
2P01HL020948-36A1
Application #
8302510
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
36
Fiscal Year
2012
Total Cost
$632,788
Indirect Cost
$234,599
Name
University of Texas Sw Medical Center Dallas
Department
Type
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
Liu, Jingjing; Moon, Young-Ah (2016) Simple Purification of Adeno-Associated Virus-DJ for Liver-Specific Gene Expression. Yonsei Med J 57:790-4
Smagris, Eriks; Gilyard, Shenise; BasuRay, Soumik et al. (2016) Inactivation of Tm6sf2, a Gene Defective in Fatty Liver Disease, Impairs Lipidation but Not Secretion of Very Low Density Lipoproteins. J Biol Chem 291:10659-76
Hwang, Seonghwan; Hartman, Isamu Z; Calhoun, Leona N et al. (2016) Contribution of Accelerated Degradation to Feedback Regulation of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase and Cholesterol Metabolism in the Liver. J Biol Chem 291:13479-94
Schumacher, Marc M; Jun, Dong-Jae; Jo, Youngah et al. (2016) Geranylgeranyl-regulated transport of the prenyltransferase UBIAD1 between membranes of the ER and Golgi. J Lipid Res 57:1286-99
Tian, Jing; Goldstein, Joseph L; Brown, Michael S (2016) Insulin induction of SREBP-1c in rodent liver requires LXRα-C/EBPβ complex. Proc Natl Acad Sci U S A 113:8182-7
Theodoropoulos, Panayotis C; Gonzales, Stephen S; Winterton, Sarah E et al. (2016) Discovery of tumor-specific irreversible inhibitors of stearoyl CoA desaturase. Nat Chem Biol 12:218-25
Bartuzi, Paulina; Billadeau, Daniel D; Favier, Robert et al. (2016) CCC- and WASH-mediated endosomal sorting of LDLR is required for normal clearance of circulating LDL. Nat Commun 7:10961
Lee, Jyh-Yeuan; Kinch, Lisa N; Borek, Dominika M et al. (2016) Crystal structure of the human sterol transporter ABCG5/ABCG8. Nature 533:561-4
Chen, Qiuyue; Denard, Bray; Lee, Ching-En et al. (2016) Inverting the Topology of a Transmembrane Protein by Regulating the Translocation of the First Transmembrane Helix. Mol Cell 63:567-78
Zhang, Yinxin; Lee, Kwang Min; Kinch, Lisa N et al. (2016) Direct Demonstration That Loop1 of Scap Binds to Loop7: A CRUCIAL EVENT IN CHOLESTEROL HOMEOSTASIS. J Biol Chem 291:12888-96

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