ALTERED PHOSPHORYLATION AND OLIGOMERIZATION OF P53 IN ADENOVIRUS TYPE12-TRANSFORMED CELLS

Loss of function of the tumor-suppressor protein p53 is, in general, e ither caused by mutation, inducing a conformational change, or by bind ing to inactivating cellular (e.g. MDM2) or viral (e.g, SV40 large T) proteins. In adenovirus type 12 (Ad12)-transformed cells, p53 is stabi lized without detectable binding to the Ad12 E1B/54 kDa protein and st ill present in a wild-type conformation but contains a mutant-like act ivity in cellular transformation, In this study we examined whether th e changed characteristics of p53 in Ad12-transformed cells are correla ted with changes in phosphorylation or complex formation of the protei n, By making tryptic phosphopeptide maps we found a significant increa se in the phosphorylation of the N-terminus of p53. Furthermore, expre ssion of E1A was found to be essential for the altered phosphorylation , while expression of only Ad12 E1B/54 kDa is sufficient to increase t he protein half-life. Additionally, we observed p53 to be present in i ncreased molecular weight complexes in Ad12-transformed cells. We conc lude that both the phosphorylation and oligomerization of p53 is chang ed as a result of Ad12 transformation.