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Journal of Virology, January 1999, p. 738-745, Vol. 73, No. 1
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Phosphorylation of the Human T-Cell Leukemia Virus Type 1 Transactivator Tax on Adjacent Serine Residues Is Critical for Tax Activation

Françoise Bex,1,* Kathy Murphy,2 Ruddy Wattiez,3 Arsène Burny,1 and Richard B. Gaynor2

Department of Molecular Biology, Université Libre de Bruxelles, B-1640 Rhode St Genèse,1 and Department of Biological Chemistry, Université de Mons-Hainaut, B-7000 Mons,3 Belgium, and Division of Molecular Virology, Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75235-85942

Received 10 August 1998/Accepted 12 October 1998

The Tax transactivator protein of human T-cell leukemia virus type 1 (HTLV-1) plays a central role in the activation of viral gene expression. In addition, Tax is capable of activating the expression of specific cellular genes and is involved in the transformation of T-lymphocytes resulting in the development of adult T-cell leukemia. Tax is a phosphoprotein that colocalizes in nuclear bodies with RNA polymerase II, splicing complexes, and specific transcription factors including members of the ATF/CREB and NF-kappa B families. In this study, we identified adjacent serine residues at positions 300 and 301 in the carboxy terminus of Tax as the major sites for phosphorylation. Phosphorylation of at least one of these serine residues is required for Tax localization in nuclear bodies and for Tax-mediated activation of gene expression via both the ATF/CREB and NF-kappa B pathways. Introduction of amino acid substitutions which are phosphoserine mimetics at positions 300 and 301 restored the ability of a phosphorylation-defective Tax mutant to form nuclear bodies and to activate gene expression. These studies define sites for regulatory phosphorylation events in Tax which are critical for its ability to activate gene transcription.

* Corresponding author. Mailing address: Département de Biologie Moléculaire, Université Libre de Bruxelles, 67, Rue des Chevaux, B-1640 Rhode St Genèse, Belgium. Phone: 32 2 6509825. Fax: 32 2 6509839. E-mail: fbex{at}dbm.ulb.ac.be.

Journal of Virology, January 1999, p. 738-745, Vol. 73, No. 1
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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