Atg7 Modulates p53 Activity to Regulate Cell Cycle and Survival During Metabolic Stress

Abstract

Starvation and Autophagy Starvation stimulates withdrawal from the cell cycle, as well as stimulating autophagy. Are these two events connected? Lee et al. (p. 225 ) show a direct and nutrient-sensitive interaction between the tumor suppressor p53 and the essential autophagy gene Atg7. Further, in the absence of Atg7, the p53-dependent induction of the cyclin-dependent kinase inhibitor p21 is inhibited. This leads to Atg7-deficient cells being unable to properly withdraw from the cell cycle under starved conditions. While Atg7 deletion leads to an impairment of p53-mediated cell-cycle arrest, the Atg7-deficient cells hyperactivate p53-mediated cell-death pathways. The physiological importance of this hyperactivation is underscored by the observation that genetic blocking of p53-mediated cell death significantly extended neonatal survival of mice in which Atg7 had been deleted.