p53 Transformation-Related Protein: Detection of an Associated Phosphotransferase Activity

Malignant cells of the mouse transformed by a variety of different agents have been found to express high levels of a 53,000 Mrphosphoprotein (designated p53). Little or no p53 can be detected in normal mouse cells. The nucleus appears to be the predominant site of p53 localization in transformed cells. p53-related antigens are also found in transformed cells of rat, hamster, rabbit, and human. In cells transformed by simian virus 40 (SV40), p53 forms a complex with SV40 tumor (T) antigen, resulting in the coprecipitation of T antigen by monoclonal p53 antibodies. Immune complexes of p53 precipitated from extracts of SV40- or methylcholanthrene-transformed cells by monoclonal p53 antibodies have protein kinase activity. This enzymatic activity is dependent upon divalent cations, utilizing Mn2+more effectively than Mn2+. The phosphorylation of p53 in this kinase reaction has been found to involve serine and threonine, but not tyrosine residues. In view of the finding that the transforming proteins of several different oncogenic viruses have kinase activity, the association of this activity with p53 is important with regard to the possibility of a common pathway of transformation by diverse agents.