HTLV-I ENCODED TAX IN ASSOCIATION WITH NF-KAPPA-B PRECURSOR P105 ENHANCES NUCLEAR-LOCALIZATION OF NF-KAPPA-B P50 AND P65 IN TRANSFECTED CELLS

NF-kappaB is a heterodimeric protein composed of two subunits, p50 and p65, and is sequestered in the cytoplasm as an inactive form through the association with an inhibitory protein, IkappaB. In the present st udy, the effect of HTLV-1 encoded Tax on the exogenously expressed NF- kappaB p105, which encodes a precursor of p50, was investigated using a COS-7 expression system. When p105 was expressed in COS-7 cells, the precursor p105 and the processed p50 were retained in the cytosolic f raction by associating each other, and p50 was not detected in the nuc lear fraction. In the cells co-expressing p105 and Tax, the p50/p105 r atio in the cytosolic fraction reduced with an induction of p50 in the nuclear fraction, which gave rise to a significant increase in NF-kap paB binding activity. Enhancement of NF-kappaB binding activity was no t observed by adenovirus encoded EIA and bovine papilloma virus encode d E2, and correlated well with the ability of Tax to associate with p1 05. When p105DELTAX which lacks the repeats of the ankyrin motif was e xpressed in this system, p105DELTAX and processed p50 were detected in the nuclear fraction and p50/p105DELTAX ratio was not affected by co- expression with Tax. In the same expression system, exogenously expres sed NF-kappaB p65 was retained in the cytoplasm by p105 and further ex pression of Tax allowed entry of p65 in the nucleus. These results sug gest that, in this model system, p105 acts as an IkappaB to sequester p50 and p65 in the cytoplasm and that Tax by inhibiting IkappaB activi ty of p105, enhances nuclear localization of p50 and p65. These findin gs raise a possibility for a novel mechanism for the induction of NF-k appaB in the nucleus by Tax.