Tet1 facilitates hypoxia tolerance by stabilizing the HIF-alpha proteins independent of its methylcytosine dioxygenase activity
Wang, Jing1; Zhang, Dawei1; Du, Juan1; Zhou, Chi1; Li, Zhi1; Liu, Xing1; Ouyang, Gang1; Xiao, Wuhan1,2,3
2017-12-15
Source PublicationNUCLEIC ACIDS RESEARCH
ISSN0305-1048
Volume45Issue:22
AbstractBecause of the requirement of oxygen (O-2) to produce energy, aerobic organisms developed mechanisms to protect themselves against a shortage of oxygen in both acute status and chronic status. To date, how organisms tolerate acute hypoxia and the underlying mechanisms remain largely unknown. Here, we identify that Tet1, one member of the ten-eleven translocation (TET) family of methylcytosine dioxygenases, is required for hypoxia tolerance in zebrafish and mice. Tet1-null zebrafish and mice are more sensitive to hypoxic conditions compared with their wild-type siblings. We demonstrate that Tet1 stabilizes hypoxia-inducible factor alpha (HIF-alpha) and enhances HIF-alpha transcription activity independent of its enzymatic activity. In addition, we show that Tet1 modulates HIF-2 alpha and HIF-1 alpha through different mechanisms. Tet1 competes with prolyl hydroxylase protein 2 (PHD2) to bind to HIF-2 alpha, resulting in a reduction of HIF-2 alpha hydroxylation by PHD2. For HIF1 alpha, however, Tet1 has no effect on HIF-1 alpha hydroxylation, but rather it appears to stabilize the C-terminus of HIF-1 alpha by affecting lysine site modification. Furthermore, we found that Tet1 enhances rather than prevents poly-ubiquitination on HIF-alpha. Our results reveal a previously unrecognized function of Tet1 independent of its methylcytosine dioxygenase activity in hypoxia signaling.
SubtypeArticle
DOI10.1093/nar/gkx869
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Indexed BySCI
Funding OrganizationChinese Academy of Sciences(XDA08010208) ; Chinese Academy of Sciences(XDA08010208) ; NSFC(31461163003 ; NSFC(31461163003 ; 91631102 ; 91631102 ; 31601051 ; 31601051 ; 31671315 ; 31671315 ; 31721005) ; 31721005) ; Chinese Academy of Sciences(XDA08010208) ; Chinese Academy of Sciences(XDA08010208) ; NSFC(31461163003 ; NSFC(31461163003 ; 91631102 ; 91631102 ; 31601051 ; 31601051 ; 31671315 ; 31671315 ; 31721005) ; 31721005)
Language英语
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS KeywordHIGH-ALTITUDE ADAPTATION ; HIPPEL-LINDAU PROTEIN ; INDUCIBLE FACTORS ; DNA DEMETHYLATION ; DEGRADATION ; TIBETAN ; CANCER ; METHYLATION ; HIF-1-ALPHA ; PHD2
WOS IDWOS:000419064400015
Funding OrganizationChinese Academy of Sciences(XDA08010208) ; Chinese Academy of Sciences(XDA08010208) ; NSFC(31461163003 ; NSFC(31461163003 ; 91631102 ; 91631102 ; 31601051 ; 31601051 ; 31671315 ; 31671315 ; 31721005) ; 31721005) ; Chinese Academy of Sciences(XDA08010208) ; Chinese Academy of Sciences(XDA08010208) ; NSFC(31461163003 ; NSFC(31461163003 ; 91631102 ; 91631102 ; 31601051 ; 31601051 ; 31671315 ; 31671315 ; 31721005) ; 31721005)
Citation statistics
Cited Times:1[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/43678
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, State Key Lab Freshwater Ecol & Biotechnol, Inst Hydrobiol, Wuhan 430072, Hubei, Peoples R China
2.Chinese Acad Sci, Key Lab Aquat Biodivers & Conservat, Inst Hydrobiol, Wuhan 430072, Hubei, Peoples R China
3.Minist Agr, Key Lab Aquaculture Dis Control, Wuhan 430072, Hubei, Peoples R China
Recommended Citation
GB/T 7714
Wang, Jing,Zhang, Dawei,Du, Juan,et al. Tet1 facilitates hypoxia tolerance by stabilizing the HIF-alpha proteins independent of its methylcytosine dioxygenase activity[J]. NUCLEIC ACIDS RESEARCH,2017,45(22).
APA Wang, Jing.,Zhang, Dawei.,Du, Juan.,Zhou, Chi.,Li, Zhi.,...&Xiao, Wuhan.(2017).Tet1 facilitates hypoxia tolerance by stabilizing the HIF-alpha proteins independent of its methylcytosine dioxygenase activity.NUCLEIC ACIDS RESEARCH,45(22).
MLA Wang, Jing,et al."Tet1 facilitates hypoxia tolerance by stabilizing the HIF-alpha proteins independent of its methylcytosine dioxygenase activity".NUCLEIC ACIDS RESEARCH 45.22(2017).
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