TRANS-ACTING FUNCTION OF THE V- AND C-REL ONCOPROTEINS

The v-rel oncogene of avian reticuloendotheliosis virus strain T (Rev-T), a highly oncogenic retrovirus, transforms chicken spleen and bone marrow cells in vitro and induces lethal B cell lymphomas in vivo. The mechanism by which the v-rel oncoprotein transforms cells has yet to be determined. Accumulating evidence suggest that its cellular homolog, c-rel, might contribute to lymphoid cell differentiation. The recent demonstration that the mouse and human transcription factors NFkB and KBF1 belong to the neoplastic transformation and lymphoid cell differentiation. The work described in this proposal will extend our studies on the trans- acting function of the v- and c-rel proteins by investigating the functional relationship between the products of the rel gene-family and transcription factor NFkB. Experiments are presented to define sequences responsive to the trans-acting function of rel and to map the domains of the rel proteins involved in DNA-binding, dimerization, association with cellular proteins and transactivation. The interplay between the trans- acting functions of the v- and c-rel proteins will also be examined, to clarify the mechanism by which v-rel and c-rel proteins will also be examined to clarify the mechanism by which v-rel transforms lymphoid cells. Finally, we will examine whether and how the protein-protein interactions in which v- and c-rel participate in lymphoid cells might regulate their subcellular localization and function. It these experiments indicate that the interaction of the v- and c-rel proteins with one or more specific cellular proteins plays a role in their biological effects, our future research will be directed towards cloning and characterizing the genes that encode them. These studies will not only help to define the mechanism by which v-rel transforms lymphoid cells but they will also help to clarify the function of the c-rel proto-oncogene in lymphoid cell differentiation.