Regulation of cellular metabolism and hypoxia by p53

Abstract

The p53 protein is essential for the implementation of the cellular response to challenging environmental conditions. Reacting to stochastic nutrient stress, p53 integrates the activity of key metabolite-sensing pathways to coordinate an appropriate cell response. During starvation, p53 activity augments cell survival pathways, inhibits unnecessary growth, and promotes efficient nutrient generation, utilization, and conservation. Similarly, during oxygen stress, p53 facilitates redirection of cellular metabolism toward energy generation through nonoxidative means, the suppression of reactive oxygen species (ROS) generation, and ROS detoxification-promoting cell survival. However, if adverse conditions are too acute or persistent, p53 can switch roles to implement canonical cell killing. The ability of p53 to regulate metabolism is a powerful feature of p53 biology that can both promote cell survival and act as a check on the inappropriate proliferation of cancer cells.