pubmed-article:8662666 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:8662666 | lifeskim:mentions | umls-concept:C0086418 | lld:lifeskim |
pubmed-article:8662666 | lifeskim:mentions | umls-concept:C0079460 | lld:lifeskim |
pubmed-article:8662666 | lifeskim:mentions | umls-concept:C0039194 | lld:lifeskim |
pubmed-article:8662666 | lifeskim:mentions | umls-concept:C0012854 | lld:lifeskim |
pubmed-article:8662666 | lifeskim:mentions | umls-concept:C0017262 | lld:lifeskim |
pubmed-article:8662666 | lifeskim:mentions | umls-concept:C1333104 | lld:lifeskim |
pubmed-article:8662666 | lifeskim:mentions | umls-concept:C1522492 | lld:lifeskim |
pubmed-article:8662666 | pubmed:issue | 24 | lld:pubmed |
pubmed-article:8662666 | pubmed:dateCreated | 1996-8-20 | lld:pubmed |
pubmed-article:8662666 | pubmed:abstractText | Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hemopoietic growth factor that is expressed in activated T cells, fibroblasts, macrophages, and endothelial cells. Although GM-CSF does not appear to be essential for normal hemopoiesis, overexpression of GM-CSF has been implicated in the pathogenesis of some diseases such as myeloid leukemia and chronic inflammation. An NF-kappaB/Rel binding site within the GM-CSF promoter, termed the kappaB element appears to be important for controlling expression in reporter gene assays in response to a number of stimuli in T cells. We investigated oligonucleotide-directed triple helix formation across this regulatory sequence as a potential tool to inhibit GM-CSF gene transcription. A 15-base oligonucleotide, GM3, was targeted to a purine-rich region in the GM-CSF proximal promoter, which overlaps the kappaB element. Gel mobility shift assays and DNase I footprinting demonstrated that GM3 formed a sequence-specific collinear triplex with its double-stranded DNA target. Triplex formation by GM3 blocked recombinant and nuclear NF-kappaB proteins binding to the GM-CSF element. GM3 also caused selective inhibition of the human T-cell lymphotrophic virus-1 Tax transactivator-induced luciferase activity from a reporter construct driven by the GM-CSF promoter in Jurkat T cells. Finally, GM3 greatly reduced the concentration of endogenous GM-CSF mRNA induced by different stimuli in Jurkat T cells but did not affect interleukin 3 mRNA levels in the same cells. We conclude that the kappaB element in the GM-CSF promoter plays a central role in the transcriptional activation of the endogenous GM-CSF gene. Colinear triplex formation acts as a selective transcriptional repressor of the GM-CSF gene and may have potential therapeutic application in cases of undesirable overexpression of this protein. | lld:pubmed |
pubmed-article:8662666 | pubmed:language | eng | lld:pubmed |
pubmed-article:8662666 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:8662666 | pubmed:citationSubset | IM | lld:pubmed |
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pubmed-article:8662666 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:8662666 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:8662666 | pubmed:month | Jun | lld:pubmed |
pubmed-article:8662666 | pubmed:issn | 0021-9258 | lld:pubmed |
pubmed-article:8662666 | pubmed:author | pubmed-author:ShannonM FMF | lld:pubmed |
pubmed-article:8662666 | pubmed:author | pubmed-author:KochetkovaMM | lld:pubmed |
pubmed-article:8662666 | pubmed:issnType | Print | lld:pubmed |
pubmed-article:8662666 | pubmed:day | 14 | lld:pubmed |
pubmed-article:8662666 | pubmed:volume | 271 | lld:pubmed |
pubmed-article:8662666 | pubmed:owner | NLM | lld:pubmed |
pubmed-article:8662666 | pubmed:authorsComplete | Y | lld:pubmed |
pubmed-article:8662666 | pubmed:pagination | 14438-44 | lld:pubmed |
pubmed-article:8662666 | pubmed:dateRevised | 2008-11-21 | lld:pubmed |
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pubmed-article:8662666 | pubmed:year | 1996 | lld:pubmed |
pubmed-article:8662666 | pubmed:articleTitle | DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells. | lld:pubmed |
pubmed-article:8662666 | pubmed:affiliation | Division of Human Immunology, Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Frome Road, Adelaide 5000, South Australia, Australia. | lld:pubmed |
pubmed-article:8662666 | pubmed:publicationType | Journal Article | lld:pubmed |
pubmed-article:8662666 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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