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The tax protein-DNA interaction is essential for HTLV-I transactivation in vitro

Lenzmeier, Brian A. and Baird, Eldon E. and Dervan, Peter B. and Nyborg, Jennifer K. (1999) The tax protein-DNA interaction is essential for HTLV-I transactivation in vitro. Journal of Molecular Biology, 291 (4). pp. 731-44. ISSN 0022-2836. https://resolver.caltech.edu/CaltechAUTHORS:20160510-091116306

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Abstract

The human T-cell leukemia virus type-1 (HTLV-I)-encoded Tax protein enhances viral gene transcription through interaction with three repeated DNA elements located in the viral promoter. These elements, called viral CREs, are composed of an off-consensus eight base-pair cyclic AMP response element (CRE), immediately flanked by sequences that are rich in guanine and cytosine residues. Recent biochemical experiments have demonstrated that in the presence of the cellular protein CREB, Tax directly binds the viral CRE G+C-rich sequences via interaction with the minor groove. To determine the functional significance of the Tax-DNA interaction, we synthesized minor groove-binding pyrrole-imidazole polyamides which bind specifically to the G+C-rich sequences in the viral CREs. At concentrations where the polyamides specifically protect the G+C-rich sequences from MPE:Fe cleavage, the polyamides block the Tax-DNA interaction. At precisely these same concentrations, the polyamides specifically inhibit Tax transactivation in vitro, without altering CREB-activated transcription or basal transcription from the same promoter. Together, these data provide strong evidence that Tax-viral CRE interaction is essential for Tax function in vitro, and suggest that targeted disruption of the Tax-DNA minor groove interaction with polyamides may provide a novel approach for inhibiting viral replication in vivo.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1006/jmbi.1999.2969DOIArticle
http://www.sciencedirect.com/science/article/pii/S0022283699929698PublisherArticle
ORCID:
AuthorORCID
Dervan, Peter B.0000-0001-8852-7306
Additional Information:© 1999 Academic Press. (Received 7 April 1999; received in revised form 9 June 1999; accepted 25 June 1999) We thank Holli Giebler for technical assistance, Dr Mark Anderson for the G-less cassette promoter templates, C.-Z. Giam and R. Harrod for the Tax point mutant expression plasmids and Joel Gottesfeld for numerous helpful discussions. This work was supported by NIH CA55035 (J.K.N.) and NIH GM51747 (P.B.D.), and a Colorado Institute for Research in Biotechnology (CIRB) fellowship for B.A.L.
Funders:
Funding AgencyGrant Number
NIHCA55035
NIHGM-51747
Colorado Institute for Research in Biotechnology (CIRB)UNSPECIFIED
Subject Keywords:polyamides; transcription; oncoprotein; CBP; CREB
Issue or Number:4
Record Number:CaltechAUTHORS:20160510-091116306
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160510-091116306
Official Citation:Brian A Lenzmeier, Eldon E Baird, Peter B Dervan, Jennifer K Nyborg, The tax protein-DNA interaction is essential for HTLV-I transactivation in Vitro1, Journal of Molecular Biology, Volume 291, Issue 4, 27 August 1999, Pages 731-744, ISSN 0022-2836, http://dx.doi.org/10.1006/jmbi.1999.2969. (http://www.sciencedirect.com/science/article/pii/S0022283699929698)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:66852
Collection:CaltechAUTHORS
Deposited By: Victoria Brennan
Deposited On:18 May 2016 19:40
Last Modified:26 Nov 2019 11:15

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