Forkhead Transcription Factor 3a (FOXO3a) Modulates Hypoxia Signaling via Up-regulation of the von Hippel-Lindau Gene (VHL)
Liu, Xing1; Cai, Xiaolian1; Hu, Bo1; Mei, Zhichao1; Zhang, Dawei1; Ouyang, Gang1; Wang, Jing1; Zhang, Wei1; Xiao, Wuhan1,2
2016-12-02
Source PublicationJOURNAL OF BIOLOGICAL CHEMISTRY
ISSN0021-9258
Volume291Issue:49Pages:25692-25705
AbstractFOXO3a, a member of the forkhead homeobox type O (FOXO) family of transcriptional factors, regulates cell survival in response to DNA damage, caloric restriction, and oxidative stress. The von Hippel-Lindau (VHL) tumor suppressor gene encodes a component of the E3 ubiquitin ligase complex that mediates hypoxia-inducible factor degradation under aerobic conditions, thus acting as one of the key regulators of hypoxia signaling. However, whether FOXO3a impacts cellular hypoxia stress remains unknown. Here we show that FOXO3a directly binds to the VHL promoter and up-regulates VHL expression. Using a zebrafish model, we confirmed the up-regulation of vhl by foxo3b, an ortholog of mammalian FOXO3a. Furthermore, by employing the clustered regularly interspaced short palindromic repeats (CRISPR)-associated RNA-guided endonuclease Cas9 (CRISPR/Cas9) technology, we deleted foxo3b in zebrafish and determined that expression of hypoxia-inducible genes was affected under hypoxia. Moreover, foxo3b-null zebrafish exhibited impaired acute hypoxic tolerance, resulting in death. In conclusion, our findings suggest that, by modulating hypoxia-inducible factor activity via up-regulation of VHL, FOXO3a (foxo3b) plays an important role in survival in response to hypoxic stress.
SubtypeArticle
KeywordFoxo Hypoxia Hypoxia-inducible Factor (Hif) Stress Transcription Regulation Zebrafish Pvhl
DOI10.1074/jbc.M116.745471
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Indexed BySCI
Funding OrganizationNational Natural Science Foundation in China (NSFC)(31401072) ; National Natural Science Foundation in China (NSFC)(31401072) ; Chinese Academy of Sciences Major Scientific and Technological Project(XDA08010208) ; Chinese Academy of Sciences Major Scientific and Technological Project(XDA08010208) ; NSFC(31461163003 ; NSFC(31461163003 ; 91631102 ; 91631102 ; 31671315) ; 31671315) ; National Natural Science Foundation in China (NSFC)(31401072) ; National Natural Science Foundation in China (NSFC)(31401072) ; Chinese Academy of Sciences Major Scientific and Technological Project(XDA08010208) ; Chinese Academy of Sciences Major Scientific and Technological Project(XDA08010208) ; NSFC(31461163003 ; NSFC(31461163003 ; 91631102 ; 91631102 ; 31671315) ; 31671315)
Language英语
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS KeywordHIGH-ALTITUDE ADAPTATION ; CELL RENAL-CARCINOMA ; OXIDATIVE STRESS ; HIF-ALPHA ; PROTEASOMAL DEGRADATION ; INDUCIBLE FACTORS ; BETA-CATENIN ; PVHL ; PROTEIN ; PATHWAY
WOS IDWOS:000390095300034
Funding OrganizationNational Natural Science Foundation in China (NSFC)(31401072) ; National Natural Science Foundation in China (NSFC)(31401072) ; Chinese Academy of Sciences Major Scientific and Technological Project(XDA08010208) ; Chinese Academy of Sciences Major Scientific and Technological Project(XDA08010208) ; NSFC(31461163003 ; NSFC(31461163003 ; 91631102 ; 91631102 ; 31671315) ; 31671315) ; National Natural Science Foundation in China (NSFC)(31401072) ; National Natural Science Foundation in China (NSFC)(31401072) ; Chinese Academy of Sciences Major Scientific and Technological Project(XDA08010208) ; Chinese Academy of Sciences Major Scientific and Technological Project(XDA08010208) ; NSFC(31461163003 ; NSFC(31461163003 ; 91631102 ; 91631102 ; 31671315) ; 31671315)
Citation statistics
Cited Times:6[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/28771
Collection藻类生物学及应用研究中心_水生生物分子与细胞生物学研究中心
Affiliation1.Chinese Acad Sci, Key Lab Aquat Biodivers & Conservat, Inst Hydrobiol, Wuhan 430072, Peoples R China
2.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China
Recommended Citation
GB/T 7714
Liu, Xing,Cai, Xiaolian,Hu, Bo,et al. Forkhead Transcription Factor 3a (FOXO3a) Modulates Hypoxia Signaling via Up-regulation of the von Hippel-Lindau Gene (VHL)[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2016,291(49):25692-25705.
APA Liu, Xing.,Cai, Xiaolian.,Hu, Bo.,Mei, Zhichao.,Zhang, Dawei.,...&Xiao, Wuhan.(2016).Forkhead Transcription Factor 3a (FOXO3a) Modulates Hypoxia Signaling via Up-regulation of the von Hippel-Lindau Gene (VHL).JOURNAL OF BIOLOGICAL CHEMISTRY,291(49),25692-25705.
MLA Liu, Xing,et al."Forkhead Transcription Factor 3a (FOXO3a) Modulates Hypoxia Signaling via Up-regulation of the von Hippel-Lindau Gene (VHL)".JOURNAL OF BIOLOGICAL CHEMISTRY 291.49(2016):25692-25705.
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