Metabolic sensing by p53: Keeping the balance between life and death

Abstract

There is no life without stress, and there is no life without mechanisms for adaptation to stress. Stress perturbs the balance of a living system, thereby scrutinizing the plasticity of its regulatory networks. These networks shape the composition and behavior of living systems. Biological networks serve the adaptability of the whole system, wherein multiple sensors and effectors cooperate to achieve maximal efficiency. Such interlacing cooperation needs to be controlled in relays (effectors) that integrate incoming signals and direct outgoing signals. The list of such powerful cellular effectors is short. In multicellular organisms, proteins of the p53 family (1) are well-studied examples of such effectors; as transcriptional factors, they balance the regulation of cell fate between proliferation, differentiation, and death. p53 is a relatively short-lived protein whose stability is regulated by multiple counteracting mechanisms targeting p53 to, or preventing it from, ubiquitin-dependent (2) or -independent (3) proteasomal degradation. The article by Khutornenko et al. (4) in PNAS reports a surprising connection between p53 stabilization (activation) in cancer cells and mitochondrial function.