IHB OpenIR  > 水生生物分子与细胞生物学研究中心  > 期刊论文
Repression of hypoxia-inducible factor alpha signaling by Set7-mediated methylation
Liu, Xing1,2; Chen, Zhu2,3; Xu, Chenxi1,2; Leng, Xiaoqian1,2; Cao, Hong1,2; Ouyang, Gang2; Xiao, Wuhan1,2; Xiao, WH (reprint author), Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China.
2015-05-26
Source PublicationNUCLEIC ACIDS RESEARCH
ISSN0305-1048
Volume43Issue:10Pages:5081-5098
AbstractHypoxia-inducible factor (HIF)-1 alpha and HIF-2 alpha are the main regulators of cellular responses to hypoxia. Post-translational modifications of HIF-1 alpha and 2 alpha are necessary to modulate their functions. The methylation of non-histone proteins by Set7, an SET domain-containing lysine methyltransferase, is a novel regulatory mechanism to control cell protein function in response to various cellular stresses. In this study, we show that Set7 methylates HIF-1 alpha at lysine 32 and HIF-2 alpha at lysine K29; this methylation inhibits the expression of HIF-1 alpha/2 alpha targets by impairing the occupancy of HIF-alpha on hypoxia response element of HIF target gene promoter. Set7-null fibroblasts and the cells with shRNA-knocked down Set7 exhibit upregulated HIF target genes. Set7 inhibitor blocks HIF-1 alpha/2 alpha methylation to enhance HIF target gene expression. Set7-null fibroblasts and the cells with shRNA-knocked down Set7 or inhibition of Set7 by the inhibitor subjected to hypoxia display an increased glucose uptake and intracellular adenosine triphosphate levels. These findings define a novel modification of HIF-1 alpha/2 alpha and demonstrate that Set7-medited lysine methylation negatively regulates HIF-alpha transcriptional activity and HIF-1 alpha-mediated glucose homeostasis.
SubtypeArticle
Department[Liu, Xing ; Xu, Chenxi ; Leng, Xiaoqian ; Cao, Hong ; Xiao, Wuhan] Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China ; [Liu, Xing ; Chen, Zhu ; Xu, Chenxi ; Leng, Xiaoqian ; Cao, Hong ; Ouyang, Gang ; Xiao, Wuhan] Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan 430072, Peoples R China ; [Chen, Zhu] Maternal & Child Hlth Hosp Hubei Prov, Dept Reprod, Wuhan, Peoples R China
DOI10.1093/nar/gkv379
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS IDWOS:000355929200029
WOS KeywordTUMOR-SUPPRESSOR PROTEIN ; INDUCED CELL-DEATH ; LYSINE METHYLATION ; TRANSCRIPTIONAL ACTIVITY ; SET9-MEDIATED METHYLATION ; PHOSPHORYLATION SWITCH ; STABILIZES HIF-1-ALPHA ; HISTONE DEMETHYLASES ; NONHISTONE PROTEINS ; GLUCOSE-METABOLISM
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Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/23970
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, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China.
Affiliation1.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China
2.Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan 430072, Peoples R China
3.Maternal & Child Hlth Hosp Hubei Prov, Dept Reprod, Wuhan, Peoples R China
Recommended Citation
GB/T 7714
Liu, Xing,Chen, Zhu,Xu, Chenxi,et al. Repression of hypoxia-inducible factor alpha signaling by Set7-mediated methylation[J]. NUCLEIC ACIDS RESEARCH,2015,43(10):5081-5098.
APA Liu, Xing.,Chen, Zhu.,Xu, Chenxi.,Leng, Xiaoqian.,Cao, Hong.,...&Xiao, WH .(2015).Repression of hypoxia-inducible factor alpha signaling by Set7-mediated methylation.NUCLEIC ACIDS RESEARCH,43(10),5081-5098.
MLA Liu, Xing,et al."Repression of hypoxia-inducible factor alpha signaling by Set7-mediated methylation".NUCLEIC ACIDS RESEARCH 43.10(2015):5081-5098.
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