NEOPLASTIC TRANSFORMATION BY RAS ONCOGENES

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We propose to investigate the molecular basis by which mutations in the ras oncogenes cause neoplastic transformation. We will take advantage of the high conservation of the ras genes during evolution and we will use Drosophila as a model system to study this problem. We will construct in vitro an altered Drosophila ras gene containing a missense mutation in the same amino acid that causes the appearance of tumors in humans. This mutant gene will be introduced into Drosophila embryos by P element-mediated transformation. We expect that this dominant mutation will give rise to tumors in the flies or some other visible phenotype. We will then isolate mutants that revert this phenotype. This mutant will either have reversed the mutation in the ras gene or will have a new mutation affecting a different gene whose protein product interacts with the p21 ras-encoded protein. We will then isolate this gene and study the biochemical and physiological characteristics of the protein product it encodes. We expect that this information will help us to understand the role of p21 in the physiology of the cell and how an alteration in its amino acid sequence gives rise to cell transformation. (X)