Journal article
Interaction between TGFβ Signaling Proteins and C/EBP Controls Basal and Tat-Mediated Transcription of HIV-1 LTR in Astrocytes
Virology (New York, N.Y.), v 299(2), pp 240-247
01 Aug 2002
PMID: 12202226
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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 TGFβ-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/EBPβ, 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/EBPβ, suggesting that interaction of C/EBPβ with Smad-3 and Smad-4 may have a negative impact upon C/EBPβ-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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Details
- Title
- Interaction between TGFβ Signaling Proteins and C/EBP Controls Basal and Tat-Mediated Transcription of HIV-1 LTR in Astrocytes
- Creators
- Jacquelyn Coyle-Rink - Temple UniversityThersa M. Sweet - Temple UniversitySelvajothi Abraham - Temple UniversityBassel E. Sawaya - Temple UniversityOlcay Batuman - SUNY Downstate Health Sciences UniversityKamel Khalili - Temple UniversityShohreh Amini - Temple University
- Publication Details
- Virology (New York, N.Y.), v 299(2), pp 240-247
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Epidemiology and Biostatistics
- Web of Science ID
- WOS:000177784800010
- Scopus ID
- 2-s2.0-0035984289
- Other Identifier
- 991021463678404721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Virology