This program studies oncogenes and papillomaviruses. Oncogene studies have involved ras and EGFR. To identify cellular ras targets, we have made mutants with changed phenotype in a previously determined effector domain of p21-ras protein and mapped the region of p21-ras with which GAP (GTPase activating protein). which is a cellular protein, interacts to this effector domain. The results suggest that GAP may be a target of p21-ras. Experiments with a full-length EGF receptor proto-oncogene placed in a retrovirus vector have shown that increased numbers of EGF receptors can contribute to the transformed phenotype. EGF can serve as a competence and progression factor in cells with high numbers of EGF receptors. In papillomavirus studies, BPV E2 protein has been shown to bind to a specific motif present several times in BPV and other PVs. This motif is an enhancer whose activity depends upon E2. Enhancement requires two or more copies of the motif. Anti-E2 sera have detected three E2 protein products in BPV transformed cells. The smaller forms of E2, which may competitively inhibit enhancement by the full-length E2 product, contain the DNA binding activity but lacks enhancer activity. The E7 ORF of HPV-16 is the principal viral transforming gene for NIH 3T3 cells. These results support the hypothosis that E7 can contribute to the transformed phenotype in human tumors.
