VIRAL AND CELLULAR ONCOGENES--MECHANISM OF ACTION

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The overall goal is to elucidate the mechanism whereby specific oncogenes contribute to the subversion of a cell from normal growth to transformed behavior. Oncogene function will be investigated at the molecular, cellular and whole organism level. The research emphasis of component projects are as follow: Subproject 1. Shenk will study the mechanism of adenovirus E1B transforming protein action. He will also explore the mechanism whereby adeno-associated virus inhibits the oncogenic activity of adenoviruses. Subproject 2. Flint will identify cellular and viral proteins and/or nucleic acids with which the adenovirus E1A and E1B transforming proteins interact. She will also employ recombinant retroviruses as vectors to introduce individual adenovirus proteins into mammalian cells to probe their individual activities. Subproject 3. Cole and Silver will map the chromosomal location of genes which determine resistance or susceptibility to plasmacytoma induction in the mouse, and then attempt to clone the relevant genetic loci. They will also employ a recombinanat retrovirus carrying the murine c-myc gene to study strain specificity of plasmacytoma induction. Subproject 4. Broach will conduct a genetic and physiological study of the yeast RAS 1 and RAS 2 genes to determine the role these genes play in the normal growth of a single eukaryotic cell. Subproject 5. Levine will utilize a cloned, murine p53 cDNA to study the structure, function and regulation of the p53 cellular tumor antigen. Levine and Gilboa will construct recombinant retroviruses which contain and express the murine p53 gene. Levine and Schedl will investigate Drosophila sequences which show strong homology to the murine p53 gene. Subproject 6. Hogan will employ photochemical probes to explore site specific variation of DNA structure within the transcriptional control regions of the adenovirus E1A and mouse c-myc genes. He will attempt to relate structure variation to control of E1A and c-myc expression.