Our program will focus on the molecular mechanisms of oncogenesis by two complementary groups of transforming proteins. The first group consists of intranuclear proteins that regulate growth properties of cells, such as immortalization and serum requirements, and alter transcriptional patterns of cells by unknown mechanisms. Projects 2, 4, 5, and 6 will investigate important representatives of these proteins. The second group consists of membrane-associated transforming proteins that have protein kinase and receptor-like activities. Projects 1 and 3 will investigate two of these transforming proteins directly, and Project 7 will deal with the receptor problem using well-characterized viral systems. An increased understanding of the activities of the intranuclear and membrane-associated transforming proteins may establish a common link between these functional groups. The specific topics of these related studies are: Project 1 - Investigations of the functional activity of the cellular src gene, Project 2 - Target cell selection by the myc gene of avian acute leukemia viruses, Project 3 - Mechanisms of action of the erb-B oncogene, Project 4 - Cis and Trans regulation of adenovirus transcription, Project 5 - In vitro studies of adeno-associated virus excision and DNA replication, Project 6 - Characterization of the SV40 early promoter-operator region, and Project 7 - Characterization of the poliovirus and adenovirus receptors.
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