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The treatment of cancer with chemotherapy or radiation therapy is limited by the emergence of tumor cells resistant to these therapies. This resistance limits our ability to successfully treat these neoplasms. A major genetic event that occurs in the genesis and/or progression of cancer is alteration in the pathway of apoptosis. Recent studies indicate that the susceptibility of cancer cells to therapy-induced death is controlled in part by genes that regulate the apoptosis pathway. In this proposal, we propose experiments (1) to determine the mechanism involved in bcl-x(s) mediated apoptosis of cancer cells using the bcl-x(s) adenovirus to dissect molecular interactions of the bcl-2 regulatory pathway and (2) to characterize cellular proteins that interact with bcl-x(s) using biochemical and genetic approaches.