Correlation of metabolic stability and altered quaternary structure of oncoprotein p53 with cell transformation

The phosphoprotein p53 seems to be implicated in various processes connected with cell transformation and in particular with the regulation of cell cycle and probably DNA replication. In the present paper we have analyzed two sets of closely related cell lines expressing the same p53 which exhibited either a nontransformed or a transformed phenotype. These cell lines were used to study biochemical properties of the p53 protein which might be correlated with cell transformation. We found a positive correlation among an elevated stability of p53, the formation of high-molecular-weight forms of p53, and the transformed phenotype of the corresponding cell lines. Furthermore, these data indicate that self-aggregation prevents p53 from rapid degradation. By a comparative analysis of the stability and oligomerization properties of mutant p53 and wild-type p53, we could demonstrate that elevated stability and self-aggregation of p53 are correlated with the transformed phenotype of the cells and independent of a particular mutation in the p53 gene.