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• W2031697457 startingPage "12765" @default.
• W2031697457 abstract "Sequence-specific pyrrole-imidazole polyamides can be designed to interfere with transcription factor binding and to regulate gene expression, both <i>in vitro</i> and in living cells. Polyamides bound adjacent to the recognition sites for TBP, Ets-1, and LEF-1 in the human immunodeficiency virus, type 1 (HIV-1), long terminal repeat inhibited transcription in cell-free assays and viral replication in human peripheral blood lymphocytes. The DNA binding activity of the transcription factor Ets-1 is specifically inhibited by a polyamide bound in the minor groove. Ets-1 is a member of the winged-helix-turn-helix family of transcription factors and binds DNA through a recognition helix bound in the major groove with additional phosphate contacts on either side of this major groove interaction. The inhibitory polyamide possibly interferes with phosphate contacts made by Ets-1, by occupying the adjacent minor groove. Full-length Ets-1 binds the HIV-1 enhancer through cooperative interactions with the p50 subunit of NF-κB, and the Ets-inhibitory polyamide also blocks formation of ternary Ets-1·NF-κB·DNA complexes on the HIV-1 enhancer. A polyamide bound adjacent to the recognition site for NF-κB also inhibits NF-κB binding and ternary complex formation. These results broaden the application range of minor groove-binding polyamides and demonstrate that these DNA ligands are powerful inhibitors of DNA-binding proteins that predominantly use major groove contacts and of cooperative protein-DNA ternary complexes." @default.
• W2031697457 created "2016-06-24" @default.
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• W2031697457 date "1999-04-01" @default.
• W2031697457 modified "2023-10-16" @default.
• W2031697457 title "Inhibition of Ets-1 DNA Binding and Ternary Complex Formation between Ets-1, NF-κB, and DNA by a Designed DNA-binding Ligand" @default.
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• W2031697457 doi "https://doi.org/10.1074/jbc.274.18.12765" @default.
• W2031697457 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/10212261" @default.
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