Linked Life Data

10224053

Source:http://linkedlifedata.com/resource/pubmed/id/10224053

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
1999-6-3
pubmed:abstractText
Sterol regulation of gene expression in mammalian cells is mediated by an interaction between the cholesterol-sensitive sterol regulatory element-binding proteins (SREBPs) and promoter-specific but generic co-regulatory transcription factors such as Sp1 and NF-Y/CBF. Thus, sterol-regulated promoters that require different co-regulatory factors could be regulated independently through targeting the specific interaction between the SREBPs and the individual co-regulatory proteins. In the present studies we demonstrate that transiently expressed yin yang 1 protein (YY1) inhibits the SREBP-mediated activation of the low density lipoprotein (LDL) receptor in a sensitive and dose-dependent manner. The inhibition is independent of YY1 binding directly to the LDL receptor promoter, and we show that the same region of YY1 that interacts in solution with Sp1 also interacts with SREBP. Furthermore, other SREBP-regulated genes that are not co-regulated by Sp1 are either not affected at all or are not as sensitive to the repression. Thus, the specific interaction that occurs between SREBPs and Sp1 to stimulate the LDL receptor promoter is a specific target for inhibition by the YY1 protein, and we provide evidence that the mechanism can be at least partially explained by the ability of YY1 to inhibit the interaction between SREBP and Sp1 in solution in vitro. The LDL receptor is the key gene of cholesterol uptake, and the rate-controlling genes of cholesterol synthesis are stimulated by the concerted action of SREBPs along with coregulators that are distinct from Sp1. Therefore, repression of gene expression through specifically targeting the interaction between SREBP and Sp1 would provide a molecular mechanism to explain how cholesterol uptake can be regulated independently from cholesterol biosynthesis in mammalian cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/CCAAT-Enhancer-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Erythroid-Specific DNA-Binding..., http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, LDL, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins, http://linkedlifedata.com/resource/pubmed/chemical/SREBF1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Sp1 Transcription Factor, http://linkedlifedata.com/resource/pubmed/chemical/Sterol Regulatory Element Binding..., http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/YY1 Transcription Factor, http://linkedlifedata.com/resource/pubmed/chemical/YY1 protein, human
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
7
pubmed:volume
274
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
13025-32
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:10224053-CCAAT-Enhancer-Binding Proteins, pubmed-meshheading:10224053-Cell Line, pubmed-meshheading:10224053-Cholesterol, pubmed-meshheading:10224053-DNA-Binding Proteins, pubmed-meshheading:10224053-Down-Regulation, pubmed-meshheading:10224053-Erythroid-Specific DNA-Binding Factors, pubmed-meshheading:10224053-Humans, pubmed-meshheading:10224053-Nuclear Proteins, pubmed-meshheading:10224053-Promoter Regions, Genetic, pubmed-meshheading:10224053-Protein Binding, pubmed-meshheading:10224053-Receptors, LDL, pubmed-meshheading:10224053-Recombinant Fusion Proteins, pubmed-meshheading:10224053-Sp1 Transcription Factor, pubmed-meshheading:10224053-Sterol Regulatory Element Binding Protein 1, pubmed-meshheading:10224053-Transcription Factors, pubmed-meshheading:10224053-YY1 Transcription Factor
pubmed:year
1999
pubmed:articleTitle
Co-stimulation of promoter for low density lipoprotein receptor gene by sterol regulatory element-binding protein and Sp1 is specifically disrupted by the yin yang 1 protein.
pubmed:affiliation
Department of Molecular Biology and Biochemistry, University of California, Irvine, California 92697, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't