http://purl.uniprot.org/citations/15247248 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/15247248 | http://www.w3.org/2000/01/rdf-schema#comment | "Insig-1 and Insig-2 are membrane proteins of the endoplasmic reticulum that regulate lipid metabolism by the following two actions: 1) sterol-induced binding to 3-hydroxy-3-methylglutaryl-coenzyme A reductase, an action that leads to ubiquitination and degradation of the enzyme; and 2) sterol-induced binding to SREBP cleavage-activating protein, an action that blocks the proteolytic processing of sterol regulatory element-binding proteins (SREBPs), membrane-bound transcription factors that enhance the synthesis of cholesterol and fatty acids. Here we report the isolation of a new mutant line of Chinese hamster ovary cells, designated SRD-14, in which Insig-1 mRNA and protein are not produced due to a partial deletion of the INSIG-1 gene. The SRD-14 cells were produced by gamma-irradiation, followed by selection with the 1,1-bisphosphonate ester SR-12813, which mimics sterols in accelerating reductase degradation but does not block SREBP processing. SRD-14 cells fail to respond to sterols by promoting reductase ubiquitination and degradation. The rate at which sterols suppress SREBP processing is significantly slower in SRD-14 cells than wild type CHO-7 cells. Sterol regulation of reductase degradation and SREBP processing is restored when SRD-14 cells are transfected with expression plasmids encoding either Insig-1 or Insig-2. These results provide formal genetic proof for the essential role of Insig-1 in feedback control of lipid synthesis in cultured cells."xsd:string |
http://purl.uniprot.org/citations/15247248 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m406406200"xsd:string |
http://purl.uniprot.org/citations/15247248 | http://purl.uniprot.org/core/author | "Lee P.C."xsd:string |
http://purl.uniprot.org/citations/15247248 | http://purl.uniprot.org/core/author | "Sever N."xsd:string |
http://purl.uniprot.org/citations/15247248 | http://purl.uniprot.org/core/author | "Song B.L."xsd:string |
http://purl.uniprot.org/citations/15247248 | http://purl.uniprot.org/core/author | "Rawson R.B."xsd:string |
http://purl.uniprot.org/citations/15247248 | http://purl.uniprot.org/core/author | "Debose-Boyd R.A."xsd:string |
http://purl.uniprot.org/citations/15247248 | http://purl.uniprot.org/core/date | "2004"xsd:gYear |
http://purl.uniprot.org/citations/15247248 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
http://purl.uniprot.org/citations/15247248 | http://purl.uniprot.org/core/pages | "43136-43147"xsd:string |
http://purl.uniprot.org/citations/15247248 | http://purl.uniprot.org/core/title | "Isolation of mutant cells lacking Insig-1 through selection with SR-12813, an agent that stimulates degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase."xsd:string |
http://purl.uniprot.org/citations/15247248 | http://purl.uniprot.org/core/volume | "279"xsd:string |
http://purl.uniprot.org/citations/15247248 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/15247248 |
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