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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

 Yeon-Soo Kim  ;  Jung-Min Kim  ;  Deug-Lim Jung  ;  Jae-Eun Kang  ;  Sukyung Lee  ;  Jin Soo Kim  ;  Wongi Seol  ;  Hyun-Chul Shin  ;  Heung Sun Kwon  ;  Carine Van Lint  ;  Nouria Hernandez  ;  Man-Wook Hur 
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.280(22) : 21545-21552, 2005 
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Tat activates transcription by interacting with Sp1, NF-kappaB, 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-inhibiting 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.
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1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jung Min(김정민)
Jung, Deug Lim(정득림)
Hur, Man Wook(허만욱) ORCID logo https://orcid.org/0000-0002-3416-1334
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