PHOSPHORYLATION OF THE HTLV-I TAX PROTEIN ON ADJACENT SERINE RESIDUES IS CRITICAL FOR TAX ACTIVITY.

Abstract

P020 The Tax transactivator protein of human T-cell leukemia virus 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 transcriptional and transforming activities are related to its ability to activate gene expression via the ATF/CREB and NF-kappaB pathways. 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-kappaB 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-kappaB 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.