PARTIALLY TRANSFORMED T3T3 CELLS EXPRESS HIGH-LEVELS OF MUTANT-P53 INTHE WILD-TYPE IMMUNOREACTIVE FORM WITH DEFECTIVE OLIGOMERIZATION

High levels of wild-type p53 suppress transformed growth of many cell lines and yet murine T3T3 cells shown partially transformed growth des pite high endogenous levels of phenotypically 'wild-type' p53. On sequ encing T3T3 p53 was found to encode missense mutations at codons 230 a nd 287 and, although endogenous T3T3 p53 is 'wild type', the protein a dopted the mutant phenotype when expressed in vitro. Size fractionatio n of T3T3 cell lysate indicated monomeric p53 possibly in complex with a low molecular weight protein. When expressed in vitro T3T3 p53 form ed dimers and higher order structures. Thus T3T3 cells appear (i) to d rive endogenous mutant p53 to adopt conformational epitopes characteri stic of the 'wild-type' protein, and (ii) to interfer with normal asse mbly of p53 quaternary structure. Phosphopeptide mapping of p53 from 3 T3x cells, T3T3 cells and SV3T3 cells indicated reduced amino terminal phosphorylation of the mutant p53 phenotype. Alternative splicing of p53 was also detected in 3T3x cells; similar splicing occurs in wild-t ype p53 (Han & Kulesz-Martin, 1992; Nucl. Acids Res., 20, 1979-1981) a nd a possible regulatory function is discussed.