PGC-1α, a key modulator of p53, promotes cell survival upon metabolic stress.
| Autor: | Sen N; Molecular Oncology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India., Satija YK, Das S |
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| Jazyk: | angličtina |
| Zdroj: | Molecular cell [Mol Cell] 2011 Nov 18; Vol. 44 (4), pp. 621-34. |
| DOI: | 10.1016/j.molcel.2011.08.044 |
| Abstrakt: | 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-1α 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-1α expression results in extensive apoptosis. Additionally, prolonged starvation results in PGC-1α 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-1α 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-1α in regulating p53-mediated cell fate decisions in response to metabolic stress. (Copyright © 2011 Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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