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SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver.
- J. Horton, J. Goldstein, Michael S Brown
- Biology, Medicine
- The Journal of clinical investigation
- 1 May 2002
The complex, interdigitated roles of these three SREBPs have been dissected through the study of ten different lines of gene-manipulated mice and form the subject of this review. Expand
Regulation of the mevalonate pathway
The mevalonate pathway produces isoprenoids that are vital for diverse cellular functions, ranging from cholesterol synthesis to growth control, and could be useful in treating certain forms of cancer as well as heart disease. Expand
A receptor-mediated pathway for cholesterol homeostasis.
The approach was to apply the techniques of cell culture to unravel the postulated regulatory defect in FH, which led to the discovery of a cell surface receptor for a plasma cholesterol transport protein called low density lipoprotein (LDL) and to the elucidation of the mechanism by which this receptor mediates feedback control of cholesterol synthesis. Expand
The SREBP Pathway: Regulation of Cholesterol Metabolism by Proteolysis of a Membrane-Bound Transcription Factor
This research was supported by grants from the National Institutes of Health (HL20948) and the Perot Family Foundation. Expand
ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs.
It is shown that S1P and S2P are required for the ER stress response as well as for lipid synthesis, and ATF6 processing did not require SCAP, which is essential for SREBP processing. Expand
Protein Sensors for Membrane Sterols
Recent advances that explain how cells employ an ensemble of membrane-embedded proteins to monitor sterol concentrations and adjust sterol synthesis and uptake are discussed. Expand
Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes
- J. Horton, N. Shah, +4 authors J. Goldstein
- Medicine, Biology
- Proceedings of the National Academy of Sciences…
- 25 September 2003
Through application of stringent combinatorial criteria, the transgenic/knockout approach allows identification of genes whose activities are likely to be controlled directly by one family of transcription factors, in this case the SREBPs. Expand
Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta.
A novel LXR target is described, the sterol regulatory element-binding protein-1c gene (SREBP-1C), which encodes a membrane-bound transcription factor of the basic helix-loop-helix-leucine zipper family and reveals a unique regulatory interplay between cholesterol and fatty acid metabolism. Expand
Identification of the Acyltransferase that Octanoylates Ghrelin, an Appetite-Stimulating Peptide Hormone
GOAT (Ghrelin O-Acyltransferase), a polytopic membrane-bound enzyme that attaches octanoate to serine-3 of ghrelin, is identified and will facilitate the search for inhibitors that reduce appetite and diminish obesity in humans. Expand
Molecular genetics of the LDL receptor gene in familial hypercholesterolemia
79 additional mutations are described and the insights that all 150 mutations have provided into the structure/function relationship of the receptor protein and the clinical manifestations of FH are reviewed. Expand