Artificial zinc finger fusions targeting Sp1-binding sites and the trans-activator-responsive element potently repress transcription and replication of HIV-1

Kim, Y. S., Kim, J. M., Jung, D. L., Kang, J. E., Lee, S., Kim, J. S., Seol, W., Shin, H. C., Kwon, H. S., Van Lint, C., Hernandez, N., Hur, M. W. (June 2005) Artificial zinc finger fusions targeting Sp1-binding sites and the trans-activator-responsive element potently repress transcription and replication of HIV-1. Journal of Biological Chemistry, 280 (22). pp. 21545-21552. ISSN 0021-9258

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URL: https://www.ncbi.nlm.nih.gov/pubmed/15743774
DOI: 10.1074/jbc.M414136200

Abstract

Tat activates transcription by interacting with Sp1, NF-kappa B, positive transcription elongation factor b, and trans-activator-responsive element (TAR). Tat and Sp1 play major roles in transcription by protein-protein interactions at human immunodeficiency virus, type 1 (HIV-1) long terminal repeat. Sp1 activates transcription by interacting with cyclin T1 in the absence of Tat. To disrupt the transcription activation by Tat and Sp1, we fused Sp1-inhibiting polypeptides, zinc finger polypeptide, and the TAR-binding mutant Tat (TatdMt) together. A designed or natural zinc finger and Tat mutant fusion was used to target the fusion to the key regulatory sites (GC box and TAR) on the long terminal repeat and nascent short transcripts to disrupt the molecular interaction that normally result in robust transcription. The designed zinc finger and TatdMt fusions were targeted to the TAR, and they potently repressed both transcription and replication of HIV-1. The Sp1-yinhibiting POZ domain, TatdMt, and zinc fingers are key functional domains important in repression of transcription and replication. The designed artificial zinc fingers were targeted to the high affinity Sp1-binding site, and by being fused with TatdMt and POZ domain, they strongly block both Sp1-cyclin T1-dependent transcription and Tat-dependent transcription, even in the presence of excess expressed Tat.

Item Type: Paper
Uncontrolled Keywords: human immunodeficiency virus DNA binding proteins long terminal repeat promyelocitic leukemia histone deacetylase HUMAN-CELLS TAT RNA promoter recepter
Subjects: diseases & disorders > viral diseases > HIV
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > transcription factor
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > zinc finger proteins
CSHL Authors:
Communities: CSHL labs > Hernandez lab
Depositing User: CSHL Librarian
Date: June 2005
Date Deposited: 12 Jan 2012 17:24
Last Modified: 08 May 2018 15:35
Related URLs:
URI: https://repository.cshl.edu/id/eprint/22623

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