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

Détails

ID Serval
serval:BIB_A6392E665579
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Artificial zinc finger fusions targeting Sp1-binding sites and the trans-activator-responsive element potently repress transcription and replication of HIV-1.
Périodique
Journal of Biological Chemistry
Auteur(s)
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.
ISSN
0021-9258
Statut éditorial
Publié
Date de publication
2005
Peer-reviewed
Oui
Volume
280
Numéro
22
Pages
21545-21552
Langue
anglais
Résumé
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.
Mots-clé
Binding Sites, Cell Line, Cell-Free System, Chloramphenicol O-Acetyltransferase/metabolism, Cyclins/chemistry, Gene Deletion, Gene Products, tat/metabolism, HIV, HIV-1/metabolism, Hela Cells, Humans, Models, Biological, Mutation, Peptides/chemistry, Plasmids/metabolism, Polymerase Chain Reaction, Promoter Regions, Genetic, Protein Binding, Protein Structure, Tertiary, RNA Polymerase II/chemistry, Recombinant Fusion Proteins/chemistry, Recombinant Fusion Proteins/metabolism, Sp1 Transcription Factor/metabolism, Transcription, Genetic, Transcriptional Activation, Zinc/chemistry, Zinc Fingers, tat Gene Products, Human Immunodeficiency Virus
Pubmed
Web of science
Open Access
Oui
Création de la notice
21/01/2008 17:34
Dernière modification de la notice
20/08/2019 16:11
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