Certain small and intermediate size DNA Tumor Viruses, such as the papovaviruses and the human adenoviruses, encode oncoproteins which deliver powerful signals that can seriously change the biology of mammalian cells. Among the outcomes is a state of neoplastic transformation, which can lead to tumorigenicity in a sutitable animal host. SV40 large T Ag and adenovirus E1A and two such oncoproteins, and their transforming functions are, in part, dependent upon their ability to interact with and perturb the functions of p300 and CBP, two large, closely related nuclear signal integrating and transformation suppressing proteins. In this application we will explore: i) the molecular relationships between loss of genetically defined primary murine fibroblasts; ii) the mechanisms which govern a newly discovered ability of p300/CBP to sustain mdm2-mediated p53 ubiquitination and turnover; and iii) the nature of the biochemical and biological functions of E1A/T/p53-associated p400, which turns out to be a complex of two polypeptides, TRRAP, a large C-terminal PI-3 kinase domain- containing protein, and a heretofore unrecognized member of the Swi/SNF family of chromatin remodeling proteins.
