The cellular tumour antigen p53: evidence for transformation-related, immunological variants of p53

The protein p53 is involved in the control of normal cell proliferation. However, when expressed abnormally, p53 also contributes to the process of cell transformation. The possibility that multifunctional forms of p53 exist was realised when two cell cycle dependent forms of the protein were identified in normal cells (lymphocytes: J. Milner, 1984, Nature (London) 310, 143-145). Interestingly these two forms of p53 in normal cells lack some of the epitopes recognised by monoclonal antibodies developed against p53 in transformed cells. This suggests that p53 may bear additional transformation-related epitopes in transformed cells. We have now investigated this possibility by screening a variety of cell lines for immunological variants of p53. The monoclonal antibodies PAb421, PAb122, RA3.2C2, PAb248, PAb200.47, and PAb246 were used. Our results indicate the existence of two immunologically distinct variants of p53 expressed in transformed cells. The two p53 variants are distinguished by the presence or absence of the epitope recognised by PAb246. A given cell line generally expressed a single immunological variant of p53. However, 3T6 cells expressed two subsets of p53 and appeared to modulate p53 synthesis in response to cell density.