The p53 protein was initially identified in a complex with the SV40 large T antigen in SV40-transformed rodent cells. Subsequently, p53 was shown to form complexes with adeno-virus E1B protein and the E6 protein encoded by oncogenic papillomavirus variants. Although p53 was initially considered to be a cellular proto-oncogene, it has since been classified as a tumor suppressor gene or anti-oncogene. Presumably, the presence of excess amounts of the mutant form of the protein can lead to functional inactivation of wild type p53. Mutations and allelic loss of the p53 gene have been associated with malignant transformation in a wide variety of human tumors. These findings in combination with the fact that p53 can act as a negative regulator of cell growth in normal cells suggest that the binding of p53 by various DNA tumor virus-encoded transforming proteins may be a major contributing factor to their transforming phenotype.