BIOLOGIC PROPERTIES OF NUCLEAR ONCOGENES AND ATTEMPTS TO BLOCK THEIR EFFECTS

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Recent developments in molecular biology has led to the identification of specific genetic lesions resulting in either activation or inactivation of key target genes in various tumor systems. These genes, called oncogenes, are involved in various aspects in the regulation of cell growth. It is now critical to understand the precise mechanism by which these genes function so molecular agents ultimately can be derived to alter or repress their effects. We have chosen to explore the biologic and biochemical functions of 2 dominant (L-myc and c-jun). Transcriptional and translational products of L-myc have been characterized and are now being correlated with biologic functions. Ultimately, truncated fragments of this gene will be tested for potential transformation suppression function. Likewise, we have recently described the transforming function of c-jun in mammalian cells and are now mapping this function by deletion mutation. Correlation of this function with other known activities of c-jun, such as transactivation will be done. Mutants of c-jun capable of inhibiting AP-1 strans activation and cellular transformation will be characterized.