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DC Field | Value | Language |
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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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