Linked Life Data

1968462

Source:http://linkedlifedata.com/resource/pubmed/id/1968462

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1990-4-9
pubmed:databankReference
pubmed:abstractText
We report the isolation and nucleotide sequence of the human farnesyl pyrophosphate synthetase cDNA, an enzyme in the cholesterogenic pathway. Partial cDNAs for the human farnesyl pyrophosphate synthetase were isolated by screening human hepatoma (HepG2) and placental cDNA libraries with the rat liver cDNA for farnesyl pyrophosphate synthetase as a probe. Anchored polymerase chain reaction was used to isolate the 5'-end of the cDNA. The nucleotide sequence of the human farnesyl pyrophosphate synthetase cDNA has high identity (86%) to the rat liver cDNA. Treatment of the human monocytic leukemia cell line THP-1 with phorbol esters led to 2--7-fold increases in mRNA concentrations for the three cholesterogenic enzymes, farnesyl pyrophosphate synthetase, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, and HMG-CoA synthase within 5 h. Immunoprecipitation of radiolabeled cells demonstrated that there was a corresponding increase in the rate of synthesis of all three proteins. The addition of cycloheximide to cells also led to increases in the mRNA concentrations of the three enzymes. Treatment of cells with phorbol esters and cycloheximide resulted in superinduction of all three mRNAs; HMG-CoA synthase mRNA levels increased 35-fold, farnesyl pyrophosphate synthetase 17-fold, and HMG-CoA reductase 16-fold 5 h after treatment. The mRNA levels returned to pretreatment levels by 20 h. Cells were also preincubated in the presence of a lipoprotein-deficient fraction of serum plus mevinolin to induce the levels of the three mRNAs. Addition of phorbol esters and cycloheximide to these derepressed cells led to further increases in the mRNA levels for all three enzymes. These results are consistent with the hypothesis that THP-1 cells contain a short-lived negative transcription factor which regulates transcription of the FPP synthetase, HMG-CoA reductase, and HMG-CoA synthase genes. Phorbol esters also regulate these same genes, presumably by modifying a common negative transcription factor and/or by inducing a positive transcription factor(s).
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
265
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4607-14
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:1968462-Amino Acid Sequence, pubmed-meshheading:1968462-Base Sequence, pubmed-meshheading:1968462-Carcinoma, Hepatocellular, pubmed-meshheading:1968462-Cycloheximide, pubmed-meshheading:1968462-DNA, pubmed-meshheading:1968462-DNA Probes, pubmed-meshheading:1968462-Dimethylallyltranstransferase, pubmed-meshheading:1968462-Gene Expression Regulation, pubmed-meshheading:1968462-Humans, pubmed-meshheading:1968462-Hydroxymethylglutaryl CoA Reductases, pubmed-meshheading:1968462-Hydroxymethylglutaryl-CoA Synthase, pubmed-meshheading:1968462-Liver Neoplasms, pubmed-meshheading:1968462-Molecular Sequence Data, pubmed-meshheading:1968462-Nucleic Acid Hybridization, pubmed-meshheading:1968462-Oxo-Acid-Lyases, pubmed-meshheading:1968462-Placenta, pubmed-meshheading:1968462-Polymerase Chain Reaction, pubmed-meshheading:1968462-RNA, Messenger, pubmed-meshheading:1968462-Tetradecanoylphorbol Acetate, pubmed-meshheading:1968462-Transferases, pubmed-meshheading:1968462-Tumor Cells, Cultured
pubmed:year
1990
pubmed:articleTitle
Isolation and sequence of the human farnesyl pyrophosphate synthetase cDNA. Coordinate regulation of the mRNAs for farnesyl pyrophosphate synthetase, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and 3-hydroxy-3-methylglutaryl coenzyme A synthase by phorbol ester.
pubmed:affiliation
Department of Biological Chemistry, School of Medicine, University of California, Los Angeles 90024-1679.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't