Full metadata record
DC Field | Value | Language |
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dc.contributor.author | Kim, Yunho | - |
dc.contributor.author | Nam, Hye Jin | - |
dc.contributor.author | Lee, Junyeop | - |
dc.contributor.author | Park, Do Young | - |
dc.contributor.author | Kim, Chan | - |
dc.contributor.author | Yu, Young Suk | - |
dc.contributor.author | Kim, Dongha | - |
dc.contributor.author | Park, Se Won | - |
dc.contributor.author | Bhin, Jinhyuk | - |
dc.contributor.author | Hwang, Daehee | - |
dc.contributor.author | Lee, Ho | - |
dc.contributor.author | Koh, Gou Young | - |
dc.contributor.author | Baek, Sung Hee | - |
dc.date.available | 2017-07-11T05:37:32Z | - |
dc.date.created | 2017-04-10 | - |
dc.date.issued | 2016-01 | - |
dc.identifier.issn | 2041-1723 | - |
dc.identifier.uri | http://hdl.handle.net/20.500.11750/2747 | - |
dc.description.abstract | Hypoxia-inducible factor-1 alpha (HIF-1 alpha) mediates hypoxic responses and regulates gene expression involved in angiogenesis, invasion and metabolism. Among the various HIF-1 alpha posttranslational modifications, HIF-1 alpha methylation and its physiological role have not yet been elucidated. Here we show that HIF-1 alpha is methylated by SET7/9 methyltransferase, and that lysine-specific demethylase 1 reverses its methylation. The functional consequence of HIF-1 alpha methylation is the modulation of HIF-1 alpha stability primarily in the nucleus, independent of its proline hydroxylation, during long-term hypoxic and normoxic conditions. Knock-in mice bearing a methylation-defective Hif1a(KA/KA) allele exhibit enhanced retinal angiogenesis and tumour vascularization via HIF-1 alpha stabilization. Importantly, S28Y and R30Q mutations of HIF-1 alpha, found in human cancers, are involved in the altered HIF-1 alpha stability. Together, these results demonstrate a role for HIF-1 alpha methylation in regulating protein stability, thereby modulating biological output including retinal and tumour angiogenesis, with therapeutic implications in human cancer. | - |
dc.language | English | - |
dc.publisher | Nature Publishing Group | - |
dc.title | Methylation-dependent regulation of HIF-1 alpha stability restricts retinal and tumour angiogenesis | - |
dc.type | Article | - |
dc.identifier.doi | 10.1038/ncomms10347 | - |
dc.identifier.scopusid | 2-s2.0-84955123063 | - |
dc.identifier.bibliographicCitation | Nature Communications, v.7 | - |
dc.description.isOpenAccess | TRUE | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | FACTOR-I | - |
dc.subject.keywordPlus | FACTOR 1-ALPHA | - |
dc.subject.keywordPlus | Gene | - |
dc.subject.keywordPlus | HYPOXIA-INDUCIBLE FACTOR | - |
dc.subject.keywordPlus | LIMB ISCHemIA | - |
dc.subject.keywordPlus | LYSINE DemETHYLASE LSD1 | - |
dc.subject.keywordPlus | Progenitor Cells | - |
dc.subject.keywordPlus | PROSTATE-CANCER | - |
dc.subject.keywordPlus | STem-CELLS | - |
dc.citation.title | Nature Communications | - |
dc.citation.volume | 7 | - |