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A KDM6 inhibitor potently induces ATF4 and its target gene expression through HRI activation and by UTX inhibition
https://tokushima-u.repo.nii.ac.jp/records/2009372
https://tokushima-u.repo.nii.ac.jp/records/200937243b1bf9e-3fee-49e2-8d14-7b4bc78d0933
| 名前 / ファイル | ライセンス | アクション |
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srep_11_4538.pdf (2.76 MB)
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| Item type | 文献 / Documents(1) | |||||||||||||||||||||||||||||||||||||||||||
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| 公開日 | 2021-12-02 | |||||||||||||||||||||||||||||||||||||||||||
| アクセス権 | ||||||||||||||||||||||||||||||||||||||||||||
| アクセス権 | open access | |||||||||||||||||||||||||||||||||||||||||||
| 資源タイプ | ||||||||||||||||||||||||||||||||||||||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||||||||||||||||||||||||||||||||||||||||
| 資源タイプ | journal article | |||||||||||||||||||||||||||||||||||||||||||
| 出版社版DOI | ||||||||||||||||||||||||||||||||||||||||||||
| 関連識別子 | https://doi.org/10.1038/s41598-021-83857-y | |||||||||||||||||||||||||||||||||||||||||||
| 関連名称 | 10.1038/s41598-021-83857-y | |||||||||||||||||||||||||||||||||||||||||||
| 出版タイプ | ||||||||||||||||||||||||||||||||||||||||||||
| 出版タイプ | VoR | |||||||||||||||||||||||||||||||||||||||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||||||||||||||||||||||||||||||||||||
| タイトル | ||||||||||||||||||||||||||||||||||||||||||||
| タイトル | A KDM6 inhibitor potently induces ATF4 and its target gene expression through HRI activation and by UTX inhibition | |||||||||||||||||||||||||||||||||||||||||||
| 著者 |
キタジマ, ショウジロウ
× キタジマ, ショウジロウ
× Sun, Wendi
× Lee, Kian Leong
× Ho, Jolene Caifeng
× 親泊, 政一
WEKO
305
× オカモト, タカシ
× マサイ, ヒサオ
× Poellinger, Lorenz
× カトウ, ヒロユキ
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| 内容記述 | UTX/KDM6A encodes a major histone H3 lysine 27 (H3K27) demethylase, and is frequently mutated in various types of human cancers. Although UTX appears to play a crucial role in oncogenesis, the mechanisms involved are still largely unknown. Here we show that a specific pharmacological inhibitor of H3K27 demethylases, GSK-J4, induces the expression of transcription activating factor 4 (ATF4) protein as well as the ATF4 target genes (e.g. PCK2, CHOP, REDD1, CHAC1 and TRIB3). ATF4 induction by GSK-J4 was due to neither transcriptional nor post-translational regulation. In support of this view, the ATF4 induction was almost exclusively dependent on the heme-regulated eIF2α kinase (HRI) in mouse embryonic fibroblasts (MEFs). Gene expression profiles with UTX disruption by CRISPR-Cas9 editing and the following stable re-expression of UTX showed that UTX specifically suppresses the expression of the ATF4 target genes, suggesting that UTX inhibition is at least partially responsible for the ATF4 induction. Apoptosis induction by GSK-J4 was partially and cell-type specifically correlated with the activation of ATF4-CHOP. These findings highlight that the anti-cancer drug candidate GSK-J4 strongly induces ATF4 and its target genes via HRI activation and raise a possibility that UTX might modulate cancer formation by regulating the HRI-ATF4 axis. | |||||||||||||||||||||||||||||||||||||||||||
| 書誌情報 |
en : Scientific Reports 巻 11, p. 4538, 発行日 2021-02-25 |
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| 収録物識別子タイプ | ISSN | |||||||||||||||||||||||||||||||||||||||||||
| 収録物識別子 | 20452322 | |||||||||||||||||||||||||||||||||||||||||||
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| 出版者 | Springer Nature | |||||||||||||||||||||||||||||||||||||||||||
| 権利情報 | ||||||||||||||||||||||||||||||||||||||||||||
| 権利情報 | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. | |||||||||||||||||||||||||||||||||||||||||||
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| 識別子 | 375683 | |||||||||||||||||||||||||||||||||||||||||||
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| 言語 | eng | |||||||||||||||||||||||||||||||||||||||||||
