Redox state of p63 and p73 core domains regulates sequence-specific DNA binding

In this work we report for the first time the redox sensitivity of p63 and p73 core domains to a thiol oxidizing agent azodicarboxylic acid bis[dimethylamide] (diamide). Oxidation of both p63 and p73 abolished sequence-specific binding to p53 consensus sequence, depending on the agent concentration. In the presence of specific DNA all p53 family core domains were partially protected against loss of DNA binding activity due to diamide treatment. Furthermore, we detected conditional reversibility of core domain oxidation for all p53 family members and a role of zinc ions in this process. We showed that p63 and p73 proteins had greater ability to resist the diamide oxidation in comparison with p53. Our results show p63 and p73 as redox sensitive proteins with possible functionality in response of p53 family proteins to oxidative stress.