| First Author | Sen N | Year | 2011 |
| Journal | Mol Cell | Volume | 44 |
| Issue | 4 | Pages | 621-34 |
| PubMed ID | 22099309 | Mgi Jnum | J:328019 |
| Mgi Id | MGI:6852442 | Doi | 10.1016/j.molcel.2011.08.044 |
| Citation | Sen N, et al. (2011) PGC-1alpha, a key modulator of p53, promotes cell survival upon metabolic stress. Mol Cell 44(4):621-34 |
| abstractText | 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-1alpha 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-1alpha expression results in extensive apoptosis. Additionally, prolonged starvation results in PGC-1alpha 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-1alpha 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-1alpha in regulating p53-mediated cell fate decisions in response to metabolic stress. |
