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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
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
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
A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood.
  • M. Brown, J. Goldstein
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences…
  • 28 September 1999
These regulated proteolytic cleavage reactions are ultimately responsible for controlling the level of cholesterol in membranes, cells, and blood. Expand
Binding site on macrophages that mediates uptake and degradation of acetylated low density lipoprotein, producing massive cholesterol deposition.
It is hypothesized that this macrophage uptake mechanism may mediate the degradation of denatured LDL in the body and thus serve as a "backup" mechanism for the previously described receptor-mediated degradation of native LDL that occurs in parenchymal cells. Expand
Hypercholesterolemia in low density lipoprotein receptor knockout mice and its reversal by adenovirus-mediated gene delivery.
It is concluded that the LDL receptor is responsible in part for the low levels of VLDL, IDL, and LDL in wild-type mice and that adenovirus-encoded LDL receptors can acutely reverse the hypercholesterolemic effects of LDL receptor deficiency. Expand
Receptor-mediated endocytosis of low-density lipoprotein in cultured cells.
Study of the cell surface binding, internalization, and metabolism of low-density lipoprotein (LDL) in cultured cells have provided useful information regarding the general aspects of receptor-mediated endocytosis and three classes of mutant alleles at the LDL receptor locus have been deduced. Expand
Isoform 1c of sterol regulatory element binding protein is less active than isoform 1a in livers of transgenic mice and in cultured cells.
SRE BP-1a is the most active form of SREBP-1 and that SREbp-1c may be produced when cells require a lower rate of transcription of genes regulating cholesterol and fatty acid metabolism. Expand
Activation of cholesterol synthesis in preference to fatty acid synthesis in liver and adipose tissue of transgenic mice overproducing sterol regulatory element-binding protein-2.
It is concluded that SREBP-2 is a relatively selective activator of cholesterol synthesis, as opposed to fatty acid synthesis, in liver and adipose tissue of mice. Expand