p53-mediated autophagic regulation: A prospective strategy for cancer therapy

• Nuclear p53 facilitates autophagy by transactivating its target genes.
• Cytoplasmic p53 inhibits autophagy mainly through transcription-independent, extranuclear mechanisms.
• Autophagy induced by p53 provides a prospective strategy for cancer therapy.

Autophagy is a major catabolic process that degrades and recycles cytosolic components in autophagosomes, which fuse with lysosomes. This process enables starving cells to sustain their energy requirements and metabolic states, thus facilitating their survival, especially in cancer pathogenesis. The regulation of autophagy is quite intricate. It involves a series of signaling cascades including p53, known as the best-characterized tumor suppressor protein. Recent reports have indicated that p53 plays dual roles in regulating autophagy depending on its subcellular localization. Nuclear p53 facilitates autophagy by transactivating its target genes, whereas cytoplasmic p53 mainly inhibits autophagy through extranuclear, transcription-independent mechanisms. The relationship between autophagy and neoplasia is complicated. It may be intrinsically associated with the functional status of p53, but this is not clearly elucidated. This review focuses on the role of p53 as a master regulator of autophagy. We conclude that the contextual role of autophagy in cancer, which could be switched by p53 status, is expected to be developed into a new anticancer therapeutic approach.