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고명곤

Ko, Myunggon
Cancer Epigenetics Lab.
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dc.citation.endPage 2049 -
dc.citation.number 18 -
dc.citation.startPage 2038 -
dc.citation.title GENES & DEVELOPMENT -
dc.citation.volume 26 -
dc.contributor.author Sasaki, Masato -
dc.contributor.author Knobbe, Christiane B -
dc.contributor.author Itsumi, Momoe -
dc.contributor.author Elia, Andrew J -
dc.contributor.author Harris, Isaac S -
dc.contributor.author Chio, Iok In Christine -
dc.contributor.author Cairns, Rob A -
dc.contributor.author McCracken, Susan -
dc.contributor.author Wakeham, Andrew -
dc.contributor.author Haight, Jillian -
dc.contributor.author Ten, Annick You -
dc.contributor.author Snow, Bryan -
dc.contributor.author Ueda, Takeshi -
dc.contributor.author Inoue, Satoshi -
dc.contributor.author Yamamoto, Kazuo -
dc.contributor.author Ko, Myung Gon -
dc.contributor.author Rao, Anjana -
dc.contributor.author Yen, Katharine E -
dc.contributor.author Su, Shinsan M -
dc.contributor.author Mak, Tak Wah -
dc.date.accessioned 2023-12-22T04:42:42Z -
dc.date.available 2023-12-22T04:42:42Z -
dc.date.created 2015-07-24 -
dc.date.issued 2012-09 -
dc.description.abstract Isocitrate dehydrogenase-1 (IDH1) R132 mutations occur in glioma, but their physiological significance is unknown. Here we describe the generation and characterization of brain-specific Idh1 R132H conditional knockin (KI) mice. Idh1 mutation results in hemorrhage and perinatal lethality. Surprisingly, intracellular reactive oxygen species (ROS) are attenuated in Idh1-KI brain cells despite an apparent increase in the NADP+/NADPH ratio. Idh1-KI cells also show high levels of D-2-hydroxyglutarate (D2HG) that are associated with inhibited prolyl-hydroxylation of hypoxia-inducible transcription factor-1α (Hif1α) and up-regulated Hif1α target gene transcription. Intriguingly, D2HG also blocks prolyl-hydroxylation of collagen, causing a defect in collagen protein maturation. An endoplasmic reticulum (ER) stress response induced by the accumulation of immature collagens may account for the embryonic lethality of these mutants. Importantly, D2HG-mediated impairment of collagen maturation also led to basement membrane (BM) aberrations that could play a part in glioma progression. Our study presents strong in vivo evidence that the D2HG produced by the mutant Idh1 enzyme is responsible for the above effects. © 2012 by Cold Spring Harbor Laboratory Press. -
dc.identifier.bibliographicCitation GENES & DEVELOPMENT, v.26, no.18, pp.2038 - 2049 -
dc.identifier.doi 10.1101/gad.198200.112 -
dc.identifier.issn 0890-9369 -
dc.identifier.scopusid 2-s2.0-84866480031 -
dc.identifier.uri https://scholarworks.unist.ac.kr/handle/201301/12563 -
dc.identifier.url http://genesdev.cshlp.org/content/26/18/2038.long -
dc.identifier.wosid 000308975900006 -
dc.language 영어 -
dc.publisher COLD SPRING HARBOR LAB PRESS -
dc.title D-2-hydroxyglutarate produced by mutant IDH1 perturbs collagen maturation and basement membrane function -
dc.type Article -
dc.description.journalRegisteredClass scie -
dc.description.journalRegisteredClass scopus -

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