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p53 directly suppresses BNIP3 expression to protect against hypoxia-induced cell death
Feng, Xi; Liu, Xing; Zhang, Wei; Xiao, Wuhan; 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
2011
Source PublicationEMBO JOURNAL
ISSN0261-4189
Volume30Issue:16Pages:3397-3415
AbstractHypoxia 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
KeywordApoptosis Bnip3 Hypoxia P53 Zebrafish
Department[Feng, X; Liu, X; Zhang, W; Xiao, WH] Chinese Acad Sci, Key Lab Biodivers & Conservat Aquat Organisms, Inst Hydrobiol, Wuhan 430072, Peoples R China
Subject AreaBiochemistry & Molecular Biology ; Cell Biology
Funding OrganizationNSFC[31071212, 91019008, 20890113]; National Transgene Project[2009ZX08010-021B]; CAS[KSCX2-EW-N-004-3]; NSF of Hubei Province[2008CDA012]; [2010CB126306]; [2007CB815705] ; NSFC[31071212, 91019008, 20890113]; National Transgene Project[2009ZX08010-021B]; CAS[KSCX2-EW-N-004-3]; NSF of Hubei Province[2008CDA012]; [2010CB126306]; [2007CB815705] ; NSFC[31071212, 91019008, 20890113]; National Transgene Project[2009ZX08010-021B]; CAS[KSCX2-EW-N-004-3]; NSF of Hubei Province[2008CDA012]; [2010CB126306]; [2007CB815705] ; NSFC[31071212, 91019008, 20890113]; National Transgene Project[2009ZX08010-021B]; CAS[KSCX2-EW-N-004-3]; NSF of Hubei Province[2008CDA012]; [2010CB126306]; [2007CB815705]
Indexed BySCI
Language英语
WOS IDWOS:000293971300016
Funding OrganizationNSFC[31071212, 91019008, 20890113]; National Transgene Project[2009ZX08010-021B]; CAS[KSCX2-EW-N-004-3]; NSF of Hubei Province[2008CDA012]; [2010CB126306]; [2007CB815705] ; NSFC[31071212, 91019008, 20890113]; National Transgene Project[2009ZX08010-021B]; CAS[KSCX2-EW-N-004-3]; NSF of Hubei Province[2008CDA012]; [2010CB126306]; [2007CB815705] ; NSFC[31071212, 91019008, 20890113]; National Transgene Project[2009ZX08010-021B]; CAS[KSCX2-EW-N-004-3]; NSF of Hubei Province[2008CDA012]; [2010CB126306]; [2007CB815705] ; NSFC[31071212, 91019008, 20890113]; National Transgene Project[2009ZX08010-021B]; CAS[KSCX2-EW-N-004-3]; NSF of Hubei Province[2008CDA012]; [2010CB126306]; [2007CB815705]
Citation statistics
Cited Times:58[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/16355
Collection水生生物分子与细胞生物学研究中心_期刊论文
Corresponding AuthorXiao, 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
Recommended Citation
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,Xiao, WH ,&w-xiao@ihb.ac.cn.(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.
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