| PGC-1α, a key modulator of p53, promotes cell survival upon metabolic stress. | |
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MedLine Citation:
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PMID: 22099309 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Nirmalya Sen; Yatendra Kumar Satija; Sanjeev Das |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Molecular cell Volume: 44 ISSN: 1097-4164 ISO Abbreviation: Mol. Cell Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-21 Completed Date: 2012-01-16 Revised Date: 2012-03-06 |
Medline Journal Info:
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Nlm Unique ID: 9802571 Medline TA: Mol Cell Country: United States |
Other Details:
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Languages: eng Pagination: 621-34 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Molecular Oncology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / drug effects*, genetics Cell Cycle / drug effects Cell Line, Tumor Cell Survival / drug effects, genetics Flow Cytometry Gene Silencing / drug effects Glucose / deficiency* Humans Liver / drug effects, metabolism*, pathology Mice Protein Binding RNA, Small Interfering / pharmacology Reactive Oxygen Species / metabolism Repressor Proteins / genetics, metabolism* Reverse Transcriptase Polymerase Chain Reaction Stress, Physiological / genetics* Trans-Activators / antagonists & inhibitors, genetics, metabolism* Transcriptional Activation / drug effects Tumor Suppressor Protein p53 / genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Ppargc1a protein, mouse; 0/RNA, Small Interfering; 0/Reactive Oxygen Species; 0/Repressor Proteins; 0/Trans-Activators; 0/Tumor Suppressor Protein p53; 50-99-7/Glucose; EC 6.3.2.-/Rnf2 protein, mouse |
| Comments/Corrections | |
Comment In:
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Mol Cell. 2011 Nov 18;44(4):515-6
[PMID:
22099301
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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