Mutant p53 proteins bind hsp 72/73 cellular heat shock-related proteins in SV40-transformed monkey cells

Abstract

We have examined the expression of a series of mouse mutant, as well as wild-type, p53 proteins in SV40-transformed monkey COS cells. Wild-type mouse p53 binds predominantly to SV40 large T antigen in these cells. However, several of the mutants co-precipitate exclusively with proteins of approximately 68 Kd relative molecular mass. We show by immunological and proteolytic mapping techniques that these proteins are identical to the hsp 72/73 heat shock proteins. p53 mutants in complex with hsp 72/73 have an altered subcellular location compared to the wild-type protein and the hsp 72/73 binding p53 mutants fail to exhibit an epitope recognized by monoclonal antibody PAb 246. The existence of at least two antigenically distinct subclasses of hsp 72/73 complexed to mutant p53 is shown.