Figure 3

The regulation of oxidative stress and ROS by p53. p53 exerts either antioxidant or prooxidant activity depending on extent of stress signals. Under the conditions of nonstress or low stress, p53 induces antioxidant genes, such as sestrins 1/2, TIGAR, GPX1, ALDH4, GLS2 and Parkin, to lower ROS levels in cells. Furthermore, p53 induces p21 to stabilize NRF2, a transcription factor which induces the expression of antioxidant genes to lower ROS levels. This antioxidant activity protects cells from oxidative stress-induced DNA damage and mutations, and also promotes cell survival. Under the conditions of severe stress, p53 induces prooxidant genes, including PIG3, PIG6, FDRX, Bax and Puma, to further induce ROS levels in cells, which in turn further activates p53. This prooxidant activity leads to the p53-mediated apoptosis and senescence to prevent the propagation of mutation-bearing cells. Thus, both antioxidant and prooxidant activities of p53 contribute to the role of p53 in tumor suppression.