The long range goal of this project is the analysis of the function of v-rel in lymphoid tissue. Of primary interest is the role v-rel plays in the induction of mature B-cell tumors. Experiments are designed that will define cell phenotypes that are permissive or non-permissive for v- rel-induced neoplasia. Using site-directed mutagenesis, conditional and non-conditional mutants will be constructed in the v-rel 57 kD protein. Mutant v-rel proteins will be characterized using biochemical assays for their association with in vitro kinase activity, their interaction with a 40 kD cellular protein and their location in the nuclear or cytoplasmic compartments of the infected cell. Monoclonal antibodies capable of recognizing different epitopes distributed throughout v-rel will be isolated. The mutant proteins will be characterized using the alpha v-rel monoclonal antibodies in order to analyze them for the presence of defined epitopes. Using the combined biochemical analyses of mutant v-rel proteins and the definition of structural epitopes that are associated with specific functional domains, the functional domains essential for v-rel-induced tumor development can be identified.
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