Linked Life Data

10913147

Source:http://linkedlifedata.com/resource/pubmed/id/10913147

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
39
pubmed:dateCreated
2000-10-27
pubmed:abstractText
Winged helix/forkhead (Fox) transcription factors have been implicated in the regulation of a number of insulin-responsive genes. The insulin response elements (IREs) of the phosphoenolpyruvate carboxykinase (PEPCK) and insulin-like growth factor-binding protein-1 (IGFBP-1) genes bind members of the FKHR and HNF3 subclasses of Fox proteins. Previous mutational analyses of the PEPCK and IGFBP-1 IREs revealed mutations which do not affect the binding of HNF3 proteins to these elements but do eliminate the ability of the IREs to mediate an insulin response. This dissociation of binding and function provided compelling evidence that HNF3 proteins, per se, are not insulin response proteins. The same approach was used here to determine if FKHRL1, a member of the FKHR subclass of Fox proteins, binds to the PEPCK and IGFBP-1 IREs in a manner that correlates with the ability of these elements to mediate an insulin response. Overexpression of FKHRL1 stimulates transcription from transfected reporter constructs that contain a multimerized PEPCK IRE or an IGFBP-1 IRE and this stimulation is repressed by insulin. There is a direct correlation between the ability of mutant versions of the PEPCK and IGFBP-1 IREs to bind FKHRL1 and their ability to mediate FKHRL1-induced transcription when FKHRL1 is overexpressed. However, under conditions where FKHRL1 is not overexpressed, there is a lack of correlation between FKHRL1 binding to mutant versions of the PEPCK and IGFBP-1 IREs and the ability of these elements to mediate an insulin response. Therefore, the PEPCK and IGFBP-1 IREs mediate FKHRL1-induced transcription and its inhibition by insulin when this protein is overexpressed, but at the normal cellular concentration of FKHRL1 the insulin response mediated by these elements must involve another protein.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
29
pubmed:volume
275
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
30169-75
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:10913147-Animals, pubmed-meshheading:10913147-Carboxy-Lyases, pubmed-meshheading:10913147-DNA-Binding Proteins, pubmed-meshheading:10913147-Forkhead Transcription Factors, pubmed-meshheading:10913147-Gene Expression Regulation, pubmed-meshheading:10913147-Genes, Reporter, pubmed-meshheading:10913147-Helix-Loop-Helix Motifs, pubmed-meshheading:10913147-Insulin, pubmed-meshheading:10913147-Insulin-Like Growth Factor Binding Protein 1, pubmed-meshheading:10913147-Nerve Tissue Proteins, pubmed-meshheading:10913147-Phosphorylation, pubmed-meshheading:10913147-Protein Binding, pubmed-meshheading:10913147-Rats, pubmed-meshheading:10913147-Recombinant Proteins, pubmed-meshheading:10913147-Response Elements, pubmed-meshheading:10913147-Transcription, Genetic, pubmed-meshheading:10913147-Transcription Factors, pubmed-meshheading:10913147-Tumor Cells, Cultured
pubmed:year
2000
pubmed:articleTitle
Regulation of phosphoenolpyruvate carboxykinase and insulin-like growth factor-binding protein-1 gene expression by insulin. The role of winged helix/forkhead proteins.
pubmed:affiliation
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, Tennessee 37232, USA.
pubmed:publicationType
Journal Article