Document Detail


Atg7 modulates p53 activity to regulate cell cycle and survival during metabolic stress.
MedLine Citation:
PMID:  22499945     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Withdrawal of nutrients triggers an exit from the cell division cycle, the induction of autophagy, and eventually the activation of cell death pathways. The relation, if any, among these events is not well characterized. We found that starved mouse embryonic fibroblasts lacking the essential autophagy gene product Atg7 failed to undergo cell cycle arrest. Independent of its E1-like enzymatic activity, Atg7 could bind to the tumor suppressor p53 to regulate the transcription of the gene encoding the cell cycle inhibitor p21(CDKN1A). With prolonged metabolic stress, the absence of Atg7 resulted in augmented DNA damage with increased p53-dependent apoptosis. Inhibition of the DNA damage response by deletion of the protein kinase Chk2 partially rescued postnatal lethality in Atg7(-/-) mice. Thus, when nutrients are limited, Atg7 regulates p53-dependent cell cycle and cell death pathways.
Authors:
In Hye Lee; Yoshichika Kawai; Maria M Fergusson; Ilsa I Rovira; Alexander J R Bishop; Noboru Motoyama; Liu Cao; Toren Finkel
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Science (New York, N.Y.)     Volume:  336     ISSN:  1095-9203     ISO Abbreviation:  Science     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-13     Completed Date:  2012-09-13     Revised Date:  2013-08-02    
Medline Journal Info:
Nlm Unique ID:  0404511     Medline TA:  Science     Country:  United States    
Other Details:
Languages:  eng     Pagination:  225-8     Citation Subset:  IM    
Affiliation:
Center for Molecular Medicine, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis
Autophagy
Cell Cycle
Cell Cycle Checkpoints
Cell Line, Tumor
Cells, Cultured
Cyclin-Dependent Kinase Inhibitor p21 / genetics
DNA Damage
Gene Expression Regulation
Humans
Mice
Microtubule-Associated Proteins / genetics,  metabolism*
Phosphorylation
Promoter Regions, Genetic
Protein Binding
Protein Multimerization
Protein-Serine-Threonine Kinases / genetics
Stress, Physiological*
Transcription, Genetic
Tumor Suppressor Protein p53 / metabolism*
Ubiquitin-Activating Enzymes / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/Atg7 protein, mouse; 0/Cdkn1a protein, mouse; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Microtubule-Associated Proteins; 0/Tumor Suppressor Protein p53; EC 2.7.1.11/checkpoint kinase 2; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 6.3.2.19/Atg7 protein, human; EC 6.3.2.19/Ubiquitin-Activating Enzymes
Comments/Corrections
Comment In:
Circ Res. 2012 Sep 28;111(8):962-4   [PMID:  23023507 ]
Erratum In:
Science. 2012 Aug 24;337(6097):911
Science. 2013 Aug 2;341(6145):457

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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