| The oncogene c-Myc coordinates regulation of metabolic networks to enable rapid cell cycle entry. | |
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MedLine Citation:
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PMID: 18414044 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The c-myc proto-oncogene is rapidly activated by serum and regulates genes involved in metabolism and cell cycle progression. This gene is thereby uniquely poised to coordinate both the metabolic and cell cycle regulatory events required for cell cycle entry. However, this function of Myc has not been evaluated. Using a rat fibroblast model of isogenic cell lines, myc(-/-), myc(+/-), myc(+/+) and myc(-/-) cells with an inducible c-myc transgene (mycER), we show that the Myc protein programs cells to utilize both oxidative phosphorylation and glycolysis to drive cell cycle progression. We demonstrate this coordinate regulation of metabolic networks is essential, as specific inhibitors of these pathways block Myc-induced proliferation. Metabolic events temporally correlated with cell cycle entry include increased oxygen consumption, mitochondrial function, pyruvate and lactate production, and ATP generation. Treatment of normal cells with inhibitors of oxidative phosphorylation recapitulates the myc(-/-) phenotype, resulting in impaired cell cycle entry and reduced metabolism. Combined with a kinetic expression profiling analysis of genes linked to mitochondrial function, our study indicates that Myc's ability to coordinately regulate the mitochondrial metabolic network transcriptome is required for rapid cell cycle entry. This function of Myc may underlie the pervasive presence of Myc in many human cancers. |
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Authors:
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Fionnuala Morrish; Nicola Neretti; John M Sedivy; David M Hockenbery |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural Date: 2008-02-08 |
Journal Detail:
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Title: Cell cycle (Georgetown, Tex.) Volume: 7 ISSN: 1551-4005 ISO Abbreviation: Cell Cycle Publication Date: 2008 Apr |
Date Detail:
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Created Date: 2008-05-29 Completed Date: 2008-09-03 Revised Date: 2011-03-09 |
Medline Journal Info:
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Nlm Unique ID: 101137841 Medline TA: Cell Cycle Country: United States |
Other Details:
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Languages: eng Pagination: 1054-66 Citation Subset: IM |
Affiliation:
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Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Analysis of Variance Animals Cell Cycle / physiology* Cell Line Cell Proliferation Gene Expression Profiling Glycolysis / physiology Membrane Potential, Mitochondrial Metabolic Networks and Pathways / physiology* Microarray Analysis Mitochondria / metabolism* Oxidative Phosphorylation Proto-Oncogene Proteins c-myc / genetics, metabolism* Rats Reactive Oxygen Species / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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K25 AG028753/AG/NIA NIH HHS; K25 AG028753-01A1/AG/NIA NIH HHS; R01 CA106650-02/CA/NCI NIH HHS; R01 GM041690-18/GM/NIGMS NIH HHS; R01 GM41690/GM/NIGMS NIH HHS; R01CA106650-02/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/MYC protein, human; 0/Proto-Oncogene Proteins c-myc; 0/Reactive Oxygen Species |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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