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Mol Cell Biol, April 1998, p. 2392-2405, Vol. 18, No. 4
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Differential Transcriptional Activation by Human T-Cell Leukemia Virus Type 1 Tax Mutants Is Mediated by Distinct Interactions with CREB Binding Protein and p300

Françoise Bex,1,2 Min-Jean Yin,1 Arsène Burny,2 and Richard B. Gaynor1,*

Division of Molecular Virology, Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75235-8594,1 and Department of Molecular Biology, University of Brussels, B-1640 Rhode St Genèse, Belgium2

Received 30 July 1997/Returned for modification 23 September 1997/Accepted 23 January 1998

The human T-cell leukemia virus type 1 Tax protein transforms human T lymphocytes, which can lead to the development of adult T-cell leukemia. Tax transformation is related to its ability to activate gene expression via the ATF/CREB and the NF-kappa B pathways. Transcriptional activation of these pathways is mediated by the actions of the related coactivators CREB binding protein (CBP) and p300. In this study, immunocytochemistry and confocal microscopy were used to localize CBP and p300 in cells expressing wild-type Tax or Tax mutants that are able to selectively activate gene expression from either the NF-kappa B or ATF/CREB pathway. Wild-type Tax colocalized with both CBP and p300 in nuclear bodies which also contained ATF-1 and the RelA subunit of NF-kappa B. However, a Tax mutant that selectively activates gene expression from only the ATF/CREB pathway colocalized with CBP but not p300, while a Tax mutant that selectively activates gene expression from only the NF-kappa B pathway colocalized with p300 but not CBP. In vitro and in vivo protein interaction studies indicated that the integrity of two independent domains of Tax delineated by these mutants was involved in the direct interaction of Tax with either CBP or p300. These studies are consistent with a model in which activation of either the NF-kappa B or the ATF/CREB pathway by specific Tax mutants is mediated by distinct interactions with related coactivator proteins.


* Corresponding author. Mailing address: Division of Molecular Virology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, TX 75235-8594. Phone: (214) 648-7570. Fax: (214) 648-8862. E-mail: gaynor{at}utsw.swmed.edu.




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