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题名: EAF2 Suppresses Hypoxia-Induced Factor 1 alpha Transcriptional Activity by Disrupting Its Interaction with Coactivator CBP/p300
作者: Chen, Zhu1; Liu, Xing1; Mei, Zhichao1; Wang, Zhou2; Xiao, Wuhan1
通讯作者: Xiao, WH (reprint author), Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan, Peoples R China.
关键词: INDUCIBLE FACTOR 1-ALPHA ; RENAL-CELL CARCINOMA ; GENE-EXPRESSION ; GLUCOSE-UPTAKE ; TARGET GENES ; STEM-CELLS ; SIRTUIN 1 ; HIF-2-ALPHA ; HIF-1-ALPHA ; PROTEIN
刊名: MOLECULAR AND CELLULAR BIOLOGY
发表日期: 2014-03-01
DOI: 10.1128/MCB.00718-13
卷: 34, 期:6, 页:1085-1099
收录类别: SCI
文章类型: Article
部门归属: [Chen, Zhu; Liu, Xing; Mei, Zhichao; Xiao, Wuhan] Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan, Peoples R China; [Wang, Zhou] Univ Pittsburgh, Sch Med, Inst Canc, Dept Urol, Pittsburgh, PA USA
WOS标题词: Science & Technology ; Life Sciences & Biomedicine
资助者: ABC 973 [2010CB126306]; CAS Major Scientific and Technological [XDA08010208]; NSFC [31071212, 91019008]; NIH [R37 DK51193]
类目[WOS]: Biochemistry & Molecular Biology ; Cell Biology
研究领域[WOS]: Biochemistry & Molecular Biology ; Cell Biology
摘要: Previous studies revealed that the potential tumor suppressor EAF2 binds to and stabilizes pVHL, suggesting that EAF2 may function by disturbing the hypoxia signaling pathway. However, the extent to which EAF2 affects hypoxia and the mechanisms underlying this activity remain largely unknown. In this study, we found that EAF2 is a hypoxia response gene harboring the hypoxia response element (HRE) in its promoter. By taking advantage of the pVHL-null cell lines RCC4 and 786-O, we demonstrated that hypoxia-induced factor 1 alpha (HIF-1 alpha), but not HIF-2 alpha, induced EAF2 under hypoxia. Subsequent experiments showed that EAF2 bound to and suppressed HIF-1 alpha but not HIF-2 alpha transactivity. In addition, we observed that EAF2 inhibition of HIF-1 activity resulted from the disruption of p300 recruitment and that this occurred independently of FIH-1 (factor inhibiting HIF-1) and Sirt1. Furthermore, we found that EAF2 protected cells against hypoxia-induced cell death and inhibited cellular uptake of glucose under hypoxic conditions, suggesting that EAF2 indeed may act by modulating the hypoxia-signaling pathway. Our findings not only uncover a unique feedback regulation loop between EAF2 and HIF-1 alpha but also provide a novel insight into the mechanism of EAF2 tumor suppression.
英文摘要: Previous studies revealed that the potential tumor suppressor EAF2 binds to and stabilizes pVHL, suggesting that EAF2 may function by disturbing the hypoxia signaling pathway. However, the extent to which EAF2 affects hypoxia and the mechanisms underlying this activity remain largely unknown. In this study, we found that EAF2 is a hypoxia response gene harboring the hypoxia response element (HRE) in its promoter. By taking advantage of the pVHL-null cell lines RCC4 and 786-O, we demonstrated that hypoxia-induced factor 1 alpha (HIF-1 alpha), but not HIF-2 alpha, induced EAF2 under hypoxia. Subsequent experiments showed that EAF2 bound to and suppressed HIF-1 alpha but not HIF-2 alpha transactivity. In addition, we observed that EAF2 inhibition of HIF-1 activity resulted from the disruption of p300 recruitment and that this occurred independently of FIH-1 (factor inhibiting HIF-1) and Sirt1. Furthermore, we found that EAF2 protected cells against hypoxia-induced cell death and inhibited cellular uptake of glucose under hypoxic conditions, suggesting that EAF2 indeed may act by modulating the hypoxia-signaling pathway. Our findings not only uncover a unique feedback regulation loop between EAF2 and HIF-1 alpha but also provide a novel insight into the mechanism of EAF2 tumor suppression.
关键词[WOS]: INDUCIBLE FACTOR 1-ALPHA ; RENAL-CELL CARCINOMA ; GENE-EXPRESSION ; GLUCOSE-UPTAKE ; TARGET GENES ; STEM-CELLS ; SIRTUIN 1 ; HIF-2-ALPHA ; HIF-1-ALPHA ; PROTEIN
语种: 英语
WOS记录号: WOS:000331995800015
ISSN号: 0270-7306
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.ihb.ac.cn/handle/342005/20092
Appears in Collections:水生生物分子与细胞生物学研究中心_期刊论文

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作者单位: 1.Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan, Peoples R China
2.Univ Pittsburgh, Sch Med, Inst Canc, Dept Urol, Pittsburgh, PA USA
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