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

Cited 19 time in Web of Science Cited 18 time in Scopus
Authors
Kim, Yeon-Soo; Kim, Jung-Min; Jung, Deug-Lim; Kang, Jae-Eun; Lee, Sukyung; Kim, Jin-Soo; Seol, Wongi; Shin, Hyun-Chul; Kwon, Heung Sun; Van Lint, Carine; Hernandez, Nouria; Hur, Man-Wook
Issue Date
2005-06
Citation
Journal of Biological Chemistry, Vol.280 No.22, pp.21545-21552
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.
ISSN
0021-9258
URI
http://hdl.handle.net/10371/165606
DOI
https://doi.org/10.1074/jbc.m414136200
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