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식물 노화·수명 연구단
식물 노화·수명 연구단
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Methylation-dependent regulation of HIF-1α stability restricts retinal and tumour angiogenesis

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Title
Methylation-dependent regulation of HIF-1α stability restricts retinal and tumour angiogenesis
Author(s)
Kim Y.; Nam H.J.; Lee J.; Park D.Y.; Kim C.; Yu Y.S.; Kim D.; Park S.W.; Jinhyuk Bhin; Daehee Hwang; Lee H.; Koh G.Y.; Baek S.H.
Publication Date
2016-01
Journal
NATURE COMMUNICATIONS, v.7, no., pp.10347 -
Publisher
NATURE PUBLISHING GROUP
Abstract
Hypoxia-inducible factor-1α (HIF-1α) mediates hypoxic responses and regulates gene expression involved in angiogenesis, invasion and metabolism. Among the various HIF-1α posttranslational modifications, HIF-1α methylation and its physiological role have not yet been elucidated. Here we show that HIF-1α is methylated by SET7/9 methyltransferase, and that lysine-specific demethylase 1 reverses its methylation. The functional consequence of HIF-1α methylation is the modulation of HIF-1α stability primarily in the nucleus, independent of its proline hydroxylation, during long-term hypoxic and normoxic conditions. Knock-in mice bearing a methylation-defective Hif1aKA/KA allele exhibit enhanced retinal angiogenesis and tumour vascularization via HIF-1α stabilization. Importantly, S28Y and R30Q mutations of HIF-1α, found in human cancers, are involved in the altered HIF-1α stability. Together, these results demonstrate a role for HIF-1α methylation in regulating protein stability, thereby modulating biological output including retinal and tumour angiogenesis, with therapeutic implications in human cancer
URI
https://pr.ibs.re.kr/handle/8788114/2397
ISSN
2041-1723
Appears in Collections:
Center for Cardiovascular Research(혈관 연구단) > Journal Papers (저널논문)
Center for Plant Aging Research (식물 노화·수명 연구단) > Journal Papers (저널논문)
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2. Methylation-dependent Regulation.pdfDownload

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