p53 directly suppresses BNIP3 expression to protect against hypoxia-induced cell death
文献类型：期刊论文
| 作者 | Feng, Xi; Liu, Xing; Zhang, Wei; Xiao, Wuhan |
| 刊名 | EMBO JOURNAL
 |
| 出版日期 | 2011-08-17 |
| 卷号 | 30期号:16页码:3397-3415 |
| 关键词 | apoptosis BNIP3 hypoxia p53 zebrafish |
| ISSN号 | 0261-4189 |
| 通讯作者 | Xiao, WH (reprint author), Chinese Acad Sci, Key Lab Biodivers & Conservat Aquat Organisms, Inst Hydrobiol, Donghu Nanlu 7, Wuhan 430072, Peoples R China ; w-xiao@ihb.ac.cn |
| 中文摘要 | Hypoxia stabilizes the tumour suppressor p53, allowing it to function primarily as a transrepressor; however, the function of p53 during hypoxia remains unclear. In this study, we showed that p53 suppressed BNIP3 expression by directly binding to the p53-response element motif and recruiting corepressor mSin3a to the BNIP3 promoter. The DNA-binding site of p53 must remain intact for the protein to suppress the BNIP3 promoter. In addition, taking advantage of zebrafish as an in vivo model, we confirmed that zebrafish nip3a, a homologous gene of mammalian BNIP3, was indeed induced by hypoxia and p53 mutation/knockdown enhanced nip3a expression under hypoxia resulted in cell death enhancement in p53 mutant embryos. Furthermore, p53 protected against hypoxia-induced cell death mediated by p53 suppression of BNIP3 as illustrated by p53 knockdown/loss assays in both human cell lines and zebrafish model, which is in contrast to the traditional pro-apoptotic role of p53. Our results suggest a novel function of p53 in hypoxia-induced cell death, leading to the development of new treatments for ischaemic heart disease and cerebral stoke. The EMBO Journal (2011) 30, 3397-3415. doi:10.1038/emboj.2011.248; Published online 26 July 2011 |
| 英文摘要 | Hypoxia stabilizes the tumour suppressor p53, allowing it to function primarily as a transrepressor; however, the function of p53 during hypoxia remains unclear. In this study, we showed that p53 suppressed BNIP3 expression by directly binding to the p53-response element motif and recruiting corepressor mSin3a to the BNIP3 promoter. The DNA-binding site of p53 must remain intact for the protein to suppress the BNIP3 promoter. In addition, taking advantage of zebrafish as an in vivo model, we confirmed that zebrafish nip3a, a homologous gene of mammalian BNIP3, was indeed induced by hypoxia and p53 mutation/knockdown enhanced nip3a expression under hypoxia resulted in cell death enhancement in p53 mutant embryos. Furthermore, p53 protected against hypoxia-induced cell death mediated by p53 suppression of BNIP3 as illustrated by p53 knockdown/loss assays in both human cell lines and zebrafish model, which is in contrast to the traditional pro-apoptotic role of p53. Our results suggest a novel function of p53 in hypoxia-induced cell death, leading to the development of new treatments for ischaemic heart disease and cerebral stoke. The EMBO Journal (2011) 30, 3397-3415. doi:10.1038/emboj.2011.248; Published online 26 July 2011 |
| WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
| 学科主题 | Biochemistry & Molecular Biology; Cell Biology |
| 类目[WOS] | Biochemistry & Molecular Biology ; Cell Biology |
| 研究领域[WOS] | Biochemistry & Molecular Biology ; Cell Biology |
| 关键词[WOS] | WILD-TYPE P53 ; P53-MEDIATED TRANSCRIPTIONAL REPRESSION ; INDUCIBLE FACTOR 1-ALPHA ; CARDIAC MYOCYTE DEATH ; BH3-ONLY PROTEINS ; P53-DEPENDENT APOPTOSIS ; BCL-2 FAMILY ; IN-VIVO ; P53-INDUCED APOPTOSIS ; FUNCTIONAL DOMAIN |
| 收录类别 | SCI |
| 资助信息 | NSFC[31071212, 91019008, 20890113]; National Transgene Project[2009ZX08010-021B]; CAS[KSCX2-EW-N-004-3]; NSF of Hubei Province[2008CDA012]; [2010CB126306]; [2007CB815705] |
| 语种 | 英语 |
| WOS记录号 | WOS:000293971300016 |
| 公开日期 | 2011-11-09 |
| 源URL | [http://ir.ihb.ac.cn/handle/342005/16355]  |
| 专题 | 水生生物研究所_水生生物分子与细胞生物学研究中心_期刊论文 |
| 作者单位 | Chinese Acad Sci, Key Lab Biodivers & Conservat Aquat Organisms, Inst Hydrobiol, Wuhan 430072, Peoples R China |
| 推荐引用方式 GB/T 7714 | Feng, Xi,Liu, Xing,Zhang, Wei,et al. p53 directly suppresses BNIP3 expression to protect against hypoxia-induced cell death[J]. EMBO JOURNAL,2011,30(16):3397-3415. |
| APA | Feng, Xi,Liu, Xing,Zhang, Wei,&Xiao, Wuhan.(2011).p53 directly suppresses BNIP3 expression to protect against hypoxia-induced cell death.EMBO JOURNAL,30(16),3397-3415. |
| MLA | Feng, Xi,et al."p53 directly suppresses BNIP3 expression to protect against hypoxia-induced cell death".EMBO JOURNAL 30.16(2011):3397-3415. |
入库方式： OAI收割
来源：水生生物研究所
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