rdf:type |
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lifeskim:mentions |
umls-concept:C0018270,
umls-concept:C0021467,
umls-concept:C0021469,
umls-concept:C0021641,
umls-concept:C0040649,
umls-concept:C0118111,
umls-concept:C0162493,
umls-concept:C0332255,
umls-concept:C0441712,
umls-concept:C1333572,
umls-concept:C1707271
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pubmed:issue |
10
|
pubmed:dateCreated |
2000-4-3
|
pubmed:abstractText |
The forkhead rhabdomyosarcoma transcription factor (FKHR) is a promising candidate to be the transcription factor that binds to the insulin response element of the insulin-like growth factor-binding protein-1 (IGFBP-1) promoter and mediates insulin inhibition of IGFBP-1 promoter activity. Cotransfection of mouse FKHR increased IGFBP-1 promoter activity 2-3-fold in H4IIE rat hepatoma cells; insulin inhibited FKHR-stimulated promoter activity approximately 70%. A C-terminal fragment of mouse FKHR (residues 208-652) that contains the transcription activation domain fused to a Gal4 DNA binding domain potently stimulated Gal4 promoter activity. Insulin inhibited FKHR fragment-stimulated promoter activity by approximately 70%. Inhibition was abolished by coincubation with the phosphatidylinositol-3 kinase inhibitor, LY294002. The FKHR 208-652 fragment contains two consensus sites for phosphorylation by protein kinase B (PKB)/Akt, Ser-253 and Ser-316. Neither site is required for insulin inhibition of promoter activity stimulated by the FKHR fragment, and overexpression of Akt does not inhibit FKHR fragment-stimulated Gal4 promoter activity. These results suggest that insulin- and phosphatidylinositol-3 kinase-dependent phosphorylation of another site in the fragment by a kinase different from PKB/Akt inhibits transcription activation by the fragment. Phosphorylation of this site also may be involved in insulin inhibition of transcription activation by full-length FKHR, but only after phosphorylation of Ser-253 by PKB/Akt.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Akt1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Forkhead Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Foxo1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Foxo1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor Binding...,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
|
pubmed:issn |
0021-9258
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:day |
10
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pubmed:volume |
275
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7289-95
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:10702299-Animals,
pubmed-meshheading:10702299-DNA-Binding Proteins,
pubmed-meshheading:10702299-Forkhead Transcription Factors,
pubmed-meshheading:10702299-Insulin,
pubmed-meshheading:10702299-Insulin-Like Growth Factor Binding Protein 1,
pubmed-meshheading:10702299-Mice,
pubmed-meshheading:10702299-Nerve Tissue Proteins,
pubmed-meshheading:10702299-Peptide Fragments,
pubmed-meshheading:10702299-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:10702299-Phosphorylation,
pubmed-meshheading:10702299-Promoter Regions, Genetic,
pubmed-meshheading:10702299-Protein-Serine-Threonine Kinases,
pubmed-meshheading:10702299-Proto-Oncogene Proteins,
pubmed-meshheading:10702299-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:10702299-RNA, Messenger,
pubmed-meshheading:10702299-Rats,
pubmed-meshheading:10702299-Transcription Factors,
pubmed-meshheading:10702299-Transcriptional Activation
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pubmed:year |
2000
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pubmed:articleTitle |
Insulin inhibits the activation of transcription by a C-terminal fragment of the forkhead transcription factor FKHR. A mechanism for insulin inhibition of insulin-like growth factor-binding protein-1 transcription.
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pubmed:affiliation |
Growth and Development Section, Clinical Endocrinology Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA.
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pubmed:publicationType |
Journal Article
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