| Differential DNA sequence specificity and regulation of HIV-1 enhancer activity by cRel-RelA transcription factor. | |
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MedLine Citation:
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PMID: 8071349 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The cRel-RelA and NF-kappa B (p50-RelA) transcription factors bind to a kappa B-like sequence termed Rel-related proteins binding element localized in the regulatory region of the human urokinase plasminogen activator (uPA) gene. This sequence is highly conserved in murine and porcine uPA genes where it retained the ability to associate with cRel-RelA. On the other hand, NF-kappa B binding was obtained with the human and porcine elements only. Methylation interference analysis showed that NF-kappa B and cRel-RelA had identical interference patterns. Mutational analysis showed that DNA binding was highly sensitive to mutations within the decameric Rel-related proteins binding element core site. However, alterations of nucleotides flanking the decameric IgK-kappa B motif, which preferentially associated with NF-kappa B, resulted in high affinity cRel-RelA binding both in vitro and in vivo. These data demonstrate that NF-kappa B and cRel-RelA have overlapping but distinct DNA sequence specificities. Bandshift analysis with HeLa and Jurkat cell extracts or with in vitro translated proteins revealed that the SV40-, HIV-1-, and interleukin-2 receptor alpha subunit kappa B elements efficiently associated with cRel-RelA, suggesting that this heterodimer may be involved in the regulation of several genes. Cotransfection studies of HIV-1 long terminal repeat-chloramphenicol acetyltransferase reporter DNA with RelA, cRel, and p50 expression vectors were performed in COS7 and U293 cells to analyze the ability of cRel-RelA to regulate HIV-1 enhancer activity. In vivo formation of the cRel-RelA complex resulted in specific stimulation of the viral enhancer at a level comparable with that obtained with NF-kappa B. These data suggest that activation of cellular cRel-RelA may play a critical role in the regulation of HIV-1 enhancer activity. |
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Authors:
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S K Hansen; L Guerrini; F Blasi |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 269 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 1994 Sep |
Date Detail:
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Created Date: 1994-09-29 Completed Date: 1994-09-29 Revised Date: 2012-02-27 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 22230-7 Citation Subset: IM; X |
Affiliation:
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Department of Genetics and Microbiol Biology, University of Milano, Italy. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Base Sequence Binding Sites DNA, Viral / metabolism* Enhancer Elements, Genetic* HIV Long Terminal Repeat HIV-1 / genetics* Humans Molecular Sequence Data NF-kappa B / metabolism* Simian virus 40 / genetics Swine Transcription Factor RelA Transcription Factors / metabolism* Transcriptional Activation Urokinase-Type Plasminogen Activator / genetics |
| Grant Support | |
ID/Acronym/Agency:
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168//Telethon |
| Chemical | |
Reg. No./Substance:
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0/DNA, Viral; 0/NF-kappa B; 0/Transcription Factor RelA; 0/Transcription Factors; EC 3.4.21.73/Urokinase-Type Plasminogen Activator |
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