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学科主题: Biochemistry & Molecular Biology; Cell Biology
题名: p53 directly suppresses BNIP3 expression to protect against hypoxia-induced cell death
作者: Feng, Xi1; Liu, Xing1; Zhang, Wei1; Xiao, Wuhan1
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
关键词: apoptosis ; BNIP3 ; hypoxia ; p53 ; zebrafish
刊名: EMBO JOURNAL
发表日期: 2011-08-17
DOI: 10.1038/emboj.2011.248
卷: 30, 期:16, 页:3397-3415
收录类别: SCI
文章类型: Article
部门归属: [Feng, X; Liu, X; Zhang, W; Xiao, WH] Chinese Acad Sci, Key Lab Biodivers & Conservat Aquat Organisms, Inst Hydrobiol, Wuhan 430072, Peoples R China
WOS标题词: Science & Technology ; Life Sciences & Biomedicine
资助者: NSFC[31071212, 91019008, 20890113]; National Transgene Project[2009ZX08010-021B]; CAS[KSCX2-EW-N-004-3]; NSF of Hubei Province[2008CDA012]; [2010CB126306]; [2007CB815705]
类目[WOS]: Biochemistry & Molecular Biology ; Cell Biology
研究领域[WOS]: Biochemistry & Molecular Biology ; Cell Biology
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
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
语种: 英语
WOS记录号: WOS:000293971300016
ISSN号: 0261-4189
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.ihb.ac.cn/handle/342005/16355
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, Key Lab Biodivers & Conservat Aquat Organisms, Inst Hydrobiol, Wuhan 430072, Peoples R China

Recommended Citation:
Feng, Xi; Liu, Xing; Zhang, Wei; Xiao, Wuhan.p53 directly suppresses BNIP3 expression to protect against hypoxia-induced cell death,EMBO JOURNAL,2011,30(16):3397-3415
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