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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
16
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pubmed:dateCreated |
1994-12-2
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pubmed:databankReference |
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pubmed:abstractText |
Sterol-resistant CHO cells (SRD-1 cells) fail to repress sterol synthesis and LDL receptor gene transcription when incubated with 25-hydroxycholesterol. Here we trace the defect to a rearrangement in the gene encoding SREBP-2, a membrane-bound transcription factor that regulates cholesterol homeostasis. SREBP-2 is an 1139-amino acid protein that is bound to extranuclear membranes via a carboxy-terminal attachment domain. In sterol-depleted cells a protease liberates the amino-terminal fragment (approximately 480 amino acids). This fragment, which contains the transcriptional activation and bHLH-Zip domains, translocates to the nucleus. 25-Hydroxycholesterol abolishes protease activity and halts transcription. SRD-1 cells produce a soluble, truncated form of SREBP-2 (amino acids 1-460) that lacks the membrane attachment domain and activates transcription directly, bypassing the sterol-regulated proteolytic step. Although SRD-1 cells produce full-length SREBP-2 from the wild-type allele and a related transcription factor, SREBP-1, they fail to cleave both of these precursors, indicating that the truncated form of SREBP-2 down-regulates the protease through a form of end-product feedback inhibition. The current data provide genetic evidence for the previously proposed model in which cholesterol homeostasis is controlled by sterol-regulated proteolysis of a membrane-bound bHLH-Zip transcription factor.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CCAAT-Enhancer-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SREBF1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/SREBF2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Sterol Regulatory Element Binding...,
http://linkedlifedata.com/resource/pubmed/chemical/Sterol Regulatory Element Binding...,
http://linkedlifedata.com/resource/pubmed/chemical/Sterols,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0890-9369
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
8
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pubmed:geneSymbol |
SREBP-2
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1910-9
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:7958866-Amino Acid Sequence,
pubmed-meshheading:7958866-Animals,
pubmed-meshheading:7958866-Base Sequence,
pubmed-meshheading:7958866-CCAAT-Enhancer-Binding Proteins,
pubmed-meshheading:7958866-CHO Cells,
pubmed-meshheading:7958866-Cloning, Molecular,
pubmed-meshheading:7958866-Cricetinae,
pubmed-meshheading:7958866-DNA, Complementary,
pubmed-meshheading:7958866-DNA-Binding Proteins,
pubmed-meshheading:7958866-Gene Rearrangement,
pubmed-meshheading:7958866-Humans,
pubmed-meshheading:7958866-Molecular Sequence Data,
pubmed-meshheading:7958866-Mutation,
pubmed-meshheading:7958866-Nuclear Proteins,
pubmed-meshheading:7958866-Recombinant Fusion Proteins,
pubmed-meshheading:7958866-Sterol Regulatory Element Binding Protein 1,
pubmed-meshheading:7958866-Sterol Regulatory Element Binding Protein 2,
pubmed-meshheading:7958866-Sterols,
pubmed-meshheading:7958866-Transcription, Genetic,
pubmed-meshheading:7958866-Transcription Factors
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pubmed:year |
1994
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pubmed:articleTitle |
Sterol-resistant transcription in CHO cells caused by gene rearrangement that truncates SREBP-2.
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pubmed:affiliation |
Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas 75235.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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