INTERACTION OF THE V-REL ONCOPROTEIN WITH NF-KAPPA-B AND I-KAPPA-B PROTEINS - HETERODIMERS OF A TRANSFORMATION-DEFECTIVE V-REL MUTANT AND NF-KAPPA-B P52 ARE FUNCTIONAL IN-VITRO AND IN-VIVO

The v-Rel oncoprotein of the avian Rev-T retrovirus is a member of the Rel/NF-kappa B family of transcription factors. The mechanism by whic h v-Rel malignantly transforms chicken spleen cells is not precisely k nonn. To gain a better understanding of functions needed for transform ation by v-Rel, we have now characterized the activities of mutant v-R el proteins that are defective for specific protein-protein interactio ns. Mutant v-Delta NLS, which has a deletion of the primary v-Rel nucl ear localizing sequence, does not interact efficiently with I kappa B- alpha but still transforms chicken spleen cells approximately as well as wild-type v-Rel, indicating that interaction with I kappa B-alpha i s not essential for the v-Rel transforming function. A second v-Rel mu tant, v-SPW, has been shown to be defective for the formation of homod imers, DNA binding, and transformation. However, we now find that V-SP W can form functional DNA-binding heterodimers in vitro and in vivo wi th the cellular protein NF-kappa B p52. Most strikingly, coexpression of V-SPW and p52 from a retroviral vector can induce the malignant tra nsformation of chicken spleen cells, whereas expression of either prot ein alone cannot. Our results are most consistent with a model wherein Rel homodimers or heterodimers must bind DNA and alter gene expressio n in order to transform lymphoid cells.