Redox modulation of p53 conformation and sequence-specific DNA binding in vitro.

The p53 protein is a transcription factor, the function of which is abrogated by oncogenic mutations which affect a flexible domain in the central portion of p53, altering its reactivity with conformation-specific antibodies. Here we show that both conformation and sequence-specific DNA binding of p53 translated in vitro can be modulated by metal chelators and oxidizing agents. Oxidation disrupted wild-type p53 conformation and inhibited DNA binding. Conversely, reduction favored folding of p53 into the wild-type form and restored DNA binding. Redox regulation of p53 protein conformation could represent an important mechanism for the control of p53 function.