Abstract

In Years 26-30, Research Project 2 focused on the use of somatic cell genetics to discover new genes affecting the SREBP pathway. These studies will now be carried out as a part of Research Project 1. In Years 31-35, Research Project 2 will be reconfigured to focus on the molecular mechanisms for translational control and Insig-mediated degradation of HMG CoA reductase. These mechanisms will be defined using studies in cultured cells and living animals. HMG CoA reductase is the key regulated enzyme in the mevalonate pathway, which produces essential sterol and nonsterol isoprenoids required for normal cell function (Figure 1). Reductase is subject to multivalent feedback regulation, involving control at the transcriptional and post-transcriptional levels. The transcriptional control, mediated by the sterol-regulated SREBPs, is the topic of Research Project 1.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL020948-34
Application #
8106519
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2010-07-01
Budget End
2011-06-30
Support Year
34
Fiscal Year
2010
Total Cost
$600,214
Indirect Cost

  Institution

Name
University of Texas Sw Medical Center Dallas
Department
Type
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390

  Publications

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
Muse, Evan D; Yu, Shan; Edillor, Chantle R et al. (2018) Cell-specific discrimination of desmosterol and desmosterol mimetics confers selective regulation of LXR and SREBP in macrophages. Proc Natl Acad Sci U S A 115:E4680-E4689
DeBose-Boyd, Russell A; Ye, Jin (2018) SREBPs in Lipid Metabolism, Insulin Signaling, and Beyond. Trends Biochem Sci 43:358-368

Showing the most recent 10 out of 766 publications