p53, ARF, and the Control of Autophagy

The p53 and ARF genes encode well-known tumor suppressor proteins that respond to oncogenic and genotoxic signals in order to induce growth arrest or apoptosis. Recently, both of these proteins were found to be intimately tied to metabolic pathways and to play surprising roles in autophagy. Autophagy (“self-eating”) is a critical response of eukaryotic cells to stress. During this process, portions of the cytosol, including cytoplasmic organelles, are sequestered into characteristic double-membrane vesicles called autophagosomes that are delivered to the lysosome for degradation. This rather non-specific degradation process allows the cell to adapt to its bioenergetic needs and to prolong survival. The following sections will outline the evidence for a role of p53 and ARF in autophagy, the role of this pathway in cancer, and what questions remain to be answered.