Abstract

The tumor suppressor protein p53 is a transcriptor factor highly mutated in cancer. In the last decades, research has demonstrated that, in addition to its role in the nucleus, p53 has extranuclear functions in the regulation of cellular metabolism, oxidative stress, and drug response. Specifically, p53 has been shown to have a dual role in the regulation of autophagy, a cellular mechanism that allows the turnover of old and damaged proteins and organelles, as well as a key role in cancer development. Nuclear p53 increases autophagy; however, current research indicates that cytosolic p53, either in wild-type or mutated form, regulates the autophagic pathway independently and in a manner opposite from nuclear p53. In this chapter, we discuss what is known about the nuclear and cytosolic pathways induced by wild-type and p53 mutants in the regulation of autophagy and their impact on tumorigenesis. Knowledge of the signaling pathways involved in the cytosolic-nuclear interplay will help in the identification of cellular targets that might be used for the development of new cancer therapies.