The tumor suppressor p53 is mutated or inactivated by epigenetic mechanisms in more than 50% of all human cancers. In resting conditions, baseline levels of p53 reportedly contribute to the maintenance of homeostasis

by favoring anti-oxidant mechanisms and by regulating energy metabolism.1 In response to various types of stress (e.g., DNA damage, oncogene deregulation), p53 is subjected to multiple post-translational modifications that inhibit its degradation by the proteasome system, resulting in p53 accumulation at both nuclear and extranuclear sites.2 In the nucleus, p53 controls a large number of transcriptional programs, which can lead to cell cycle blockage, activation of autophagy or induction of apoptotic cell death.2 Cytoplasmic p53 has been shown to exert lethal effects by interacting with members of the BCL-2 protein family at mitochondria,3 and inhibits autophagy.4 The subcellular shuttling of p53 (from the nucleus to the cytoplasm and from the cytoplasm to mitochondria, and vice versa) is regulated by additional post-translational modifications including MDM2-mediated (poly)monoubiquitination and HAUSP-mediated deubiquitination. 2 Thus, p53 is at the hub of a complex and highly dynamic system that regulates several aspects of the cell metabolism.