A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood
TLDR
These regulated proteolytic cleavage reactions are ultimately responsible for controlling the level of cholesterol in membranes, cells, and blood.Abstract:
The integrity of cell membranes is maintained by a balance between the amount of cholesterol and the amounts of unsaturated and saturated fatty acids in phospholipids. This balance is maintained by membrane-bound transcription factors called sterol regulatory element-binding proteins (SREBPs) that activate genes encoding enzymes of cholesterol and fatty acid biosynthesis. To enhance transcription, the active NH2-terminal domains of SREBPs are released from endoplasmic reticulum membranes by two sequential cleavages. The first is catalyzed by Site-1 protease (S1P), a membrane-bound subtilisin-related serine protease that cleaves the hydrophilic loop of SREBP that projects into the endoplasmic reticulum lumen. The second cleavage, at Site-2, requires the action of S2P, a hydrophobic protein that appears to be a zinc metalloprotease. This cleavage is unusual because it occurs within a membrane-spanning domain of SREBP. Sterols block SREBP processing by inhibiting S1P. This response is mediated by SREBP cleavage-activating protein (SCAP), a regulatory protein that activates S1P and also serves as a sterol sensor, losing its activity when sterols overaccumulate in cells. These regulated proteolytic cleavage reactions are ultimately responsible for controlling the level of cholesterol in membranes, cells, and blood.read more
Citations
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MLN64 Mediates Mobilization of Lysosomal Cholesterol to Steroidogenic Mitochondria
Mei Zhang,Pei Liu,Nancy K. Dwyer,Lane K. Christenson,Toshio Fujimoto,Federico Martinez,M E Comly,John A. Hanover,E. Joan Blanchette-Mackie,Jerome F. Strauss +9 more
TL;DR: It is concluded that MLN64 participates in mobilization and utilization of lysosomal cholesterol by virtue of the START domain's role in cholesterol transport.
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MAP kinases Erk1/2 phosphorylate sterol regulatory element-binding protein (SREBP)-1a at serine 117 in vitro.
Gunther Roth,Jorg Kotzka,Lorena Kremer,Stefan Lehr,Christiane Lohaus,Helmut E. Meyer,W. Krone,Dirk Müller-Wieland +7 more
TL;DR: The data indicate that the MAP kinase-mediated effects on SREBP-1a-regulated target genes are linked to this phosphorylation site.
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SREBPs: physiology and pathophysiology of the SREBP family.
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Mir-33 regulates cell proliferation and cell cycle progression.
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Cholesterol, Reactive Oxygen Species, and the Formation of Biologically Active Mediators
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