A THRESHOLD NUCLEAR-LEVEL OF THE V-REL ONCOPROTEIN IS REQUIRED FOR TRANSFORMATION OF AVIAN LYMPHOCYTES

The net distribution of eukaryotic transcription factors between the c ytoplasm and the nucleus provides an effective mechanism for controlli ng gene expression. We have utilized cis-acting signals for both nucle ar import and nuclear export to experimentally manipulate the distribu tion of the v-Rel oncoprotein between the nucleus and the cytoplasm. T he respective abilities of the v-Rel oncoprotein to localize to the nu cleus in chicken embryo fibroblasts, to activate kappa B-dependent tra nscription in yeast, and to transform avian lymphoid cells were each m arkedly reduced by the fusion of a cis-acting nuclear export signal on to v-Rel. Our results demonstrate that a threshold nuclear function of v-Rel is required for manifestation of its oncogenic properties. In c ontrast, while increased expression of the avian I kappa B-alpha prote in was able to prevent nuclear localization of v-Rel in chicken embryo fibroblasts, coexpression of I kappa B-alpha with v-Rel in the target cell for v-Rel mediated transformation did not reduce the ability of v-Rel to transform avian lymphoid cells or alter the distribution of v -Rel between the nucleus and the cytoplasm in v-Rel-transformed cells. Our results suggest that the ability of I kappa B-alpha to inhibit nu clear localization of v-Rel is affected by cell-type specific differen ces between fibroblasts and lymphoid cells.