| EAF2 Suppresses Hypoxia-Induced Factor 1 alpha Transcriptional Activity by Disrupting Its Interaction with Coactivator CBP/p300 | |
| Chen, Zhu1; Liu, Xing1; Mei, Zhichao1; Wang, Zhou2; Xiao, Wuhan1; Xiao, WH (reprint author), Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan, Peoples R China. | |
| 2014-03-01 | |
| Source Publication | MOLECULAR AND CELLULAR BIOLOGY
 |
| ISSN | 0270-7306 |
| Volume | 34Issue:6Pages:1085-1099 |
| Abstract | 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.; 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. |
| Subtype | Article |
| Keyword | Inducible Factor 1-alpha Renal-cell Carcinoma Gene-expression Glucose-uptake Target Genes Stem-cells Sirtuin 1 Hif-2-alpha Hif-1-alpha Protein |
| Department | [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 |
| DOI | 10.1128/MCB.00718-13 |
| WOS Headings | Science & Technology ; Life Sciences & Biomedicine |
| Funding Organization | ABC 973 [2010CB126306]; CAS Major Scientific and Technological [XDA08010208]; NSFC [31071212, 91019008]; NIH [R37 DK51193] ; ABC 973 [2010CB126306]; CAS Major Scientific and Technological [XDA08010208]; NSFC [31071212, 91019008]; NIH [R37 DK51193] ; ABC 973 [2010CB126306]; CAS Major Scientific and Technological [XDA08010208]; NSFC [31071212, 91019008]; NIH [R37 DK51193] ; ABC 973 [2010CB126306]; CAS Major Scientific and Technological [XDA08010208]; NSFC [31071212, 91019008]; NIH [R37 DK51193] |
| Indexed By | SCI |
| Language | 英语 |
| WOS Research Area | Biochemistry & Molecular Biology ; Cell Biology |
| WOS Subject | Biochemistry & Molecular Biology ; Cell Biology |
| WOS ID | WOS:000331995800015 |
| WOS Keyword | INDUCIBLE FACTOR 1-ALPHA ; RENAL-CELL CARCINOMA ; GENE-EXPRESSION ; GLUCOSE-UPTAKE ; TARGET GENES ; STEM-CELLS ; SIRTUIN 1 ; HIF-2-ALPHA ; HIF-1-ALPHA ; PROTEIN |
| Funding Organization | ABC 973 [2010CB126306]; CAS Major Scientific and Technological [XDA08010208]; NSFC [31071212, 91019008]; NIH [R37 DK51193] ; ABC 973 [2010CB126306]; CAS Major Scientific and Technological [XDA08010208]; NSFC [31071212, 91019008]; NIH [R37 DK51193] ; ABC 973 [2010CB126306]; CAS Major Scientific and Technological [XDA08010208]; NSFC [31071212, 91019008]; NIH [R37 DK51193] ; ABC 973 [2010CB126306]; CAS Major Scientific and Technological [XDA08010208]; NSFC [31071212, 91019008]; NIH [R37 DK51193] |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://ir.ihb.ac.cn/handle/342005/20092 |
| Collection | 水生生物分子与细胞生物学研究中心_期刊论文 |
| Corresponding Author | Xiao, WH (reprint author), Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan, Peoples R China. |
| Affiliation | 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 |
| Recommended Citation GB/T 7714 | Chen, Zhu,Liu, Xing,Mei, Zhichao,et al. EAF2 Suppresses Hypoxia-Induced Factor 1 alpha Transcriptional Activity by Disrupting Its Interaction with Coactivator CBP/p300[J]. MOLECULAR AND CELLULAR BIOLOGY,2014,34(6):1085-1099. |
| APA | Chen, Zhu,Liu, Xing,Mei, Zhichao,Wang, Zhou,Xiao, Wuhan,&Xiao, WH .(2014).EAF2 Suppresses Hypoxia-Induced Factor 1 alpha Transcriptional Activity by Disrupting Its Interaction with Coactivator CBP/p300.MOLECULAR AND CELLULAR BIOLOGY,34(6),1085-1099. |
| MLA | Chen, Zhu,et al."EAF2 Suppresses Hypoxia-Induced Factor 1 alpha Transcriptional Activity by Disrupting Its Interaction with Coactivator CBP/p300".MOLECULAR AND CELLULAR BIOLOGY 34.6(2014):1085-1099. |
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