MULTIMER FORMATION IS NOT ESSENTIAL FOR NUCLEAR EXPORT OF HUMAN T-CELL LEUKEMIA-VIRUS TYPE-1 REX TRANSACTIVATOR PROTEIN

The Rex trans-regulatory protein of human T-cell leukemia virus type 1 (HTLV-1) is required for the nuclear export of incompletely spliced a nd unspliced viral mRNAs and is therefore essential for virus replicat ion. Rex is a nuclear phosphoprotein that directly binds to its cis ac ting Rex response element RNA target sequence and constantly shuttles between the nucleus and cytoplasm. Moreover, Rex induces nuclear accum ulation of unspliced viral RNA. Three protein domains which mediate nu clear import-RNA binding, nuclear export, and Rex oligomerization have been mapped within the 189-amino-acid Rex polypeptide. Here we identi fied a different region in the carboxy-terminal half of Rex which is a lso required for biological activity. In inactive mutants with mutatio ns that map within this region, as well as in mutants that are deficie nt in Rex-specific multimerization, Rex trans activation could be reco nstituted by fusion to a heterologous leucine zipper dimerization inte rface. The intracellular trafficking capabilities of wild-type and mut ant Rex proteins reveal that biologically inactive and multimerization -deficient Rex mutants are still efficiently translocated from the nuc leus to the cytoplasm. This observation indicates that multimerization is essential for Rex function but is not required for nuclear export. Finally, we are able to provide an improved model of the HTLV-1 Rex d omain structure.