INTERACTION OF THE HUMAN T-LYMPHOTROPIC VIRUS TYPE-1 TAX DIMER WITH CREB AND THE VIRAL 21-BASE-PAIR REPEAT

Human T-lymphotropic virus type 1 Tax interacts specifically with the cellular transcription factor CREB and the viral 21-bp repeat element to form a Tax-CREB-DNA ternary complex which mediates activation of vi ral mRNA transcription, Analyses of Tax and Tax mutants indicate that, like CREE, Tax incorporates into the ternary complex as a dimer, The ability of Tax to form a dimer is necessary for its interaction with C REB and the 21-bp element, Analyses of several Tax mutants with amino acid substitutions spanning residues 123 to 204 indicate that intersub unit Tax dimerization correlates with its ability to assemble into the ternary complex and activate transcription, Tax also enhances the DNA binding activities of specific bZip domains in vitro. The ability of Tax to enhance DNA binding of bZip proteins can be explained in part b g Tax dimerization. This activity alone is not sufficient for transact ivation. A dual amino acid substitution mutant of Tax, M47 (L319R, L32 0S), completely abrogated for activation of the human T-lymphotropic v irus type I long terminal repeat as a result of a defect in the transa ctivation domain, continues to stimulate binding of bZip proteins to D NA.