The p53 oncogene is present in elevated levels in many tumor cells. In tissue culture, p53 cooperates with an activated ras gene to transform rat fibroblasts. Furthermore, p53 is a necessary cellular component of SV40 T antigen mediated transformation. Recently, p53 was found to bind a cellular protein, hsc70. The role of p53, whether it be a critical factor in mediating transformation or whether it be a consequence of the transformed state and simply needed for growth, remains unclear. Therefore, in order to study the effects of overexpression of p53 and its interaction with T antigen and hsc70, several p53 constructs will be introduced into mouse embryos. One of these constructs encodes a mutant p53 cDNA with an in frame linker at amino acid 215 which no longers binds T antigen, but does bind hsc70 and has an increased transformation potential in tissue culture compared to its parent cDNA. The level of expression of p53 mRNA and protein and the tissue specificity will be determined. In addition, p53 transgenic mice will be mated with mice expressing T antigen to determine the effects of p53 gene product on the development of brain tumors in these transgenic mice. The levels of hsc70 in tissues expressing p53 and the interaction of these proteins will be examined in vivo using transgenic mice.
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