Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
1991-6-10
pubmed:abstractText
Sterols reduce the activity of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG-CoA reductase) transcriptionally by inhibiting the synthesis of reductase mRNA and posttranscriptionally by accelerating degradation of the enzyme. We and others have described mutant lines of Chinese hamster fibroblasts that are completely resistant to sterol-mediated repression of transcription of HMG-CoA reductase as well as two other sterol-regulated genes, HMG-CoA synthase and the low density lipoprotein (LDL) receptor. In the current studies, we show that one line of sterol-resistant mutant cells (SRD-3 cells) retains the ability to slow the degradation of HMG-CoA reductase by 7-fold in response to treatment with compactin, an inhibitor of reductase that blocks sterol synthesis. The compactin effect is reversed by exogenous sterols. Similar results were obtained with another mutant line of sterol-resistant cells (SRD-2 cells) whose defective transcriptional regulation is attributable to a different gene than that in the SRD-3 cells, as determined by complementation analysis. These data indicate that the gene products that are defective in the SRD-3 and SRD-2 cells are not required for the sterol-mediated regulation of degradation of HMG-CoA reductase. Thus, mammalian cells possess at least two genetically distinct mechanisms, one transcriptional and the other posttranscriptional, for sensing and responding to the intracellular level of sterols.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
266
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9128-34
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
Genetic distinction between sterol-mediated transcriptional and posttranscriptional control of 3-hydroxy-3-methylglutaryl-coenzyme A reductase.
pubmed:affiliation
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't