Journal
MOLECULAR CELL
Volume 44, Issue 4, Pages 621-634Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2011.08.044
Keywords
-
Categories
Funding
- Department of Biotechnology, Government of India
- NII
- Council for Scientific and Industrial Research, Government of India
Ask authors/readers for more resources
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 alpha 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 alpha expression results in extensive apoptosis. Additionally, prolonged starvation results in PGC-1 alpha 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 alpha 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 alpha in regulating p53-mediated cell fate decisions in response to metabolic stress.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available