Addition of fresh medium induces cell cycle and conformation changes in p53, a tumour suppressor protein

Abstract

Using analytical flow cytometry we have monitored changes in the conformation of p53 through the cell cycle under different conditions of cell growth. Conformational variants of murine p53 are characterized by reactivity with monoclonal antibodies PAb246, PAb248 and PAb421. In proliferating cells, p53 conformation was independent of the cell cycle. Addition of fresh medium, however, resulted in loss of p53 reactivity with PAb246 (p53-246(0]. Mutant p53, which lacks suppressor function, is also p53-246(0). Thus in SV3T3 cells p53-246(0) may reflect a change in p53 tertiary structure that is induced by growth stimulation and is compatible with the normal cell growth response. We argue that p53-246(0) and p53-246+ may exert positive and negative constraints in cell growth control. By stabilising p53-246(0) activating mutants of p53 would favour cell proliferation with dominant effect.