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Aldo-keto reductase family 1 B10 affects fatty acid synthesis by regulating the stability of acetyl-CoA carboxylase-αin breast cancer cells

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WOS被引频次:91
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成果类型:
期刊论文
作者:
Ma, Jun;Yan, Ruilan;Zu, Xuyu;Cheng, Ji-Ming;Rao, Krishna;Liao, Duan-Fang;Cao, Deliang
通讯作者:
Cao, DL
作者机构:
[Yan, Ruilan; Rao, Krishna; Ma, Jun; Zu, Xuyu; Cao, Deliang] Department of Medical Microbiology, Immunology, and Cell Biology, SimmonsCooper Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL 62702, United States
[Cheng, Ji-Ming; Rao, Krishna] Division of Hematology/Oncology, Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62702, United States
[Liao, Duan-Fang; Zu, Xuyu] Division of Pharmacoproteomics, Institute of Pharmacy and Pharmacology, Nanhua University School of Life Science and Technology, 28 Changshengxi Road, Hengyang, Hunan 421001, China
[Cao, Deliang] Dept. of Medical Microbiology, Immunology, and Cell Biology, SimmonsCooper Cancer Inst., Southern Illinois University School of Medicine, 913 N. Rutledge St., Springfield, IL 62702, United States
通讯机构:
[Cao, Deliang] So Illinois Univ, Sch Med, SimmonsCooper Canc Inst, Dept Med Microbiol, 913 N Rutledge St, Springfield, IL 62702 USA.
语种:
英文
关键词:
Aldo-keto reductases - Breast cancer cells - Cancer cell growths - Colocalize - Essential components - Fatty acid syntheses - Gel filtrations - Hepatocellular carcinomata - Immunoprecipitation - Ion exchange chromatographies - Lung carcinomata - Mammary epithelial cells - Mass spectrometry analysis - Novel functions - Novel proteins - Proteasome - Protein complexes - Pulldown assays - Sepharose - Small interfering RNAs - Ubiquitination
期刊:
Journal of Biological Chemistry
ISSN:
0021-9258
年:
2008
卷:
283
期:
6
页码:
3418-3423
文献类别:
WOS:Article;EI:Journal article (JA)
所属学科:
ESI学科类别:生物学与生物化学;WOS学科类别:Biochemistry & Molecular Biology
入藏号:
EI:20085111789407
机构署名:
本校为其他机构
院系归属:
药学与生物科学学院
摘要:
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 (∼40 kDa) bound to DEAE-Sepharose column and protein complexes (∼300 kDa) remaining in flow-through. Co-immunoprecipitation with AKR1B10 antibody and protein mass spectrometry analysis identified that AKR1B10 associates with acetyl-CoA carboxylase-α(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 colocalize 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. ©2008 by The American Society for Biochemistry and Molecular Biology, Inc.
参考文献:
Abu-Elheiga L, 2005, P NATL ACAD SCI USA, V102, P12011, DOI 10.1073/pnas.0505714102
Brownsey RW, 2006, BIOCHEM SOC T, V34, P223
Brusselmans K, 2005, CANCER RES, V65, P6719, DOI 10.1158/0008-5472.CAN-05-0571
Cao DL, 1998, J BIOL CHEM, V273, P11429, DOI 10.1074/jbc.273.19.11429
Chajes V, 2006, CANCER RES, V66, P5287, DOI 10.1158/0008-5472.CAN-05-1489

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