| Aldo-keto reductase family 1 B10 affects fatty acid synthesis by regulating the stability of acetyl-CoA carboxylase-alpha in breast cancer cells. | |
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MedLine Citation:
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PMID: 18056116 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Recent studies have demonstrated that aldo-keto reductase family 1 B10 (AKR1B10), a novel protein overexpressed in human hepatocellular carcinoma and non-small cell lung carcinoma, may facilitate cancer cell growth by detoxifying intracellular reactive carbonyls. This study presents a novel function of AKR1B10 in tumorigenic mammary epithelial cells (RAO-3), regulating fatty acid synthesis. In RAO-3 cells, Sephacryl-S 300 gel filtration and DEAE-Sepharose ion exchange chromatography demonstrated that AKR1B10 exists in two distinct forms, monomers (approximately 40 kDa) bound to DEAE-Sepharose column and protein complexes (approximately 300 kDa) remaining in flow-through. Co-immunoprecipitation with AKR1B10 antibody and protein mass spectrometry analysis identified that AKR1B10 associates with acetyl-CoA carboxylase-alpha (ACCA), a rate-limiting enzyme of de novo fatty acid synthesis. This association between AKR1B10 and ACCA proteins was further confirmed by co-immunoprecipitation with ACCA antibody and pulldown assays with recombinant AKR1B10 protein. Intracellular fluorescent studies showed that AKR1B10 and ACCA proteins co-localize in the cytoplasm of RAO-3 cells. More interestingly, small interfering RNA-mediated AKR1B10 knock down increased ACCA degradation through ubiquitination-proteasome pathway and resulted in >50% decrease of fatty acid synthesis in RAO-3 cells. These data suggest that AKR1B10 is a novel regulator of the biosynthesis of fatty acid, an essential component of the cell membrane, in breast cancer cells. |
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Authors:
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Jun Ma; Ruilan Yan; Xuyu Zu; Ji-Ming Cheng; Krishna Rao; Duan-Fang Liao; Deliang Cao |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2007-12-01 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 283 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2008 Feb |
Date Detail:
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Created Date: 2008-02-04 Completed Date: 2008-03-31 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 3418-23 Citation Subset: IM |
Affiliation:
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Department of Medical Microbiology, Immunology, and Cell Biology, SimmonsCooper Cancer Institute, Southern Illinois University School of Medicine, Springfield, Illinois 62702, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetyl-CoA Carboxylase
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chemistry*,
metabolism Aldehyde Reductase / genetics, physiology* Breast Neoplasms / metabolism* Cell Line, Tumor Cell Membrane / metabolism Cytoplasm / metabolism Fatty Acids / metabolism Gene Expression Regulation, Neoplastic* Gene Silencing Humans Proteasome Endopeptidase Complex / metabolism RNA, Small Interfering / metabolism Recombinant Proteins / chemistry Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Ubiquitin / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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CA122327/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Fatty Acids; 0/RNA, Small Interfering; 0/Recombinant Proteins; 0/Ubiquitin; EC 1.1.1.-/AKR1B10 protein, human; EC 1.1.1.21/Aldehyde Reductase; EC 3.4.25.1/Proteasome Endopeptidase Complex; EC 6.4.1.2/Acetyl-CoA Carboxylase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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