Source:http://linkedlifedata.com/resource/pubmed/id/12202226
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2002-8-30
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pubmed:abstractText |
Signal transduction pathways induced by cytokines can modulate the level of HIV-1 gene transcription and replication in a variety of cells including those from the central nervous system. Here, we investigated the effect of TGFbeta-1 signaling the factors, including Smads, on transcription of the viral LTR in human astrocytic cells. Ectopic expression of Smad-3 increased activity of the viral promoter, while its partner protein, Smad-4, caused a slight decrease in viral gene transcription. Further, Smad-4 was able to suppress transcriptional activation of the LTR by Smad-3 as well as by C/EBPbeta, another activator of LTR transcription in these cells. Results from promoter deletion experiments identified the C/EBP-binding site, which is positioned between nucleotides -114 and -102 as one of the targets for Smad-mediated regulation of the LTR. Band-shift studies showed inhibition of C/EBP binding to its target DNA in protein extract from cells overexpressing Smad-3 and Smad-4. Results from GST pull-down assay and combined immunoprecipitation/Western blot of protein extracts from human astrocytes verified the association of Smad-3 and Smad-4 with C/EBPbeta, suggesting that interaction of C/EBPbeta with Smad-3 and Smad-4 may have a negative impact upon C/EBPbeta-mediated activation of the LTR. Interestingly, Smad-4 showed no inhibitory effect on viral gene transcription in cells expressing Tat protein. However, in the presence of Smad-3, expression of Smad-4 exerted a negative effect on Tat-mediated activation of the LTR promoter. These observations pointed to the functional interplay between viral and cellular proteins in modulating LTR transcription.
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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/CCAAT-Enhancer-Binding Protein-beta,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Gene Products, tat,
http://linkedlifedata.com/resource/pubmed/chemical/SMAD3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/SMAD4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Smad3 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Smad4 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/tat Gene Products, Human...
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0042-6822
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
299
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
240-7
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:12202226-Astrocytes,
pubmed-meshheading:12202226-CCAAT-Enhancer-Binding Protein-beta,
pubmed-meshheading:12202226-DNA-Binding Proteins,
pubmed-meshheading:12202226-Gene Products, tat,
pubmed-meshheading:12202226-HIV Long Terminal Repeat,
pubmed-meshheading:12202226-HIV-1,
pubmed-meshheading:12202226-Humans,
pubmed-meshheading:12202226-Smad3 Protein,
pubmed-meshheading:12202226-Smad4 Protein,
pubmed-meshheading:12202226-Trans-Activators,
pubmed-meshheading:12202226-Transcription, Genetic,
pubmed-meshheading:12202226-Transforming Growth Factor beta,
pubmed-meshheading:12202226-tat Gene Products, Human Immunodeficiency Virus
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pubmed:year |
2002
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pubmed:articleTitle |
Interaction between TGFbeta signaling proteins and C/EBP controls basal and Tat-mediated transcription of HIV-1 LTR in astrocytes.
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pubmed:affiliation |
Center for Neurovirology and Cancer Biology, College of Science and Technology, Temple University, 1900 North 12th Street, 015-96, Room 203, Philadelphia, PA 19122, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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