REDOX MODULATION OF P53 CONFORMATION AND SEQUENCE-SPECIFIC DNA-BINDING IN-VITRO

The p53 protein is a transcription factor, the function of which is ab rogated by oncogenic mutations which affect a flexible domain in the c entral portion of p53, altering its reactivity with conformation-speci fic antibodies. Here we show that both conformation and sequence-speci fic DNA binding of p53 translated in vitro can be modulated by metal c helators and oxidizing agents. Oxidation disrupted wild-type p53 confo rmation and inhibited DNA binding. Conversely, reduction favored foldi ng of p53 into the wild-type form and restored DNA binding. Redox regu lation of p53 protein conformation could represent an important mechan ism for the control of p53 function.