文摘
Summary
Metabolic stress results in p53 activation, which can trigger cell-cycle arrest, ROS clearance, or apoptosis. However, what determines the p53-mediated cell fate decision upon metabolic stress is not very well understood. We show here that PGC-1¦Á binds to p53 and modulates its transactivation function, resulting in preferential transactivation of proarrest and metabolic target genes. Thus glucose starvation results in p53-dependent cell-cycle arrest and ROS clearance, but abrogation of PGC-1¦Á expression results in extensive apoptosis. Additionally, prolonged starvation results in PGC-1¦Á degradation concomitant with induction of apoptosis. We have also identified RNF2, a Polycomb group (PcG) protein, as the?cognate E3 ubiquitin ligase. Starvation of mice where PGC-1¦Á expression is abrogated results in loss of p53-mediated ROS clearance, enhanced p53-dependent apoptosis, and consequent severe liver atrophy. These findings provide key insights into the role of PGC-1¦Á in regulating p53-mediated cell fate decisions in response to metabolic stress.
