| アイテムタイプ |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2025-12-08 |
| タイトル |
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タイトル |
Hydroxyurea modulates thiol–disulfide homeostasis in the yeast endoplasmic reticulum |
| 言語 |
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言語 |
eng |
| 資源タイプ |
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資源タイプ |
journal article |
| アクセス権 |
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アクセス権 |
open access |
| 著者 |
Takano, Yuki
木俣, 有紀
Ushioda, Ryo
木俣, 行雄
Nakatsukasa, Kunio
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| 抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
Hydroxyurea (HU) has been extensively used in laboratory settings to induce S-phase arrest and checkpoint activation. Furthermore, it has a history of clinical use as a cost-effective chemotherapeutic agent. Nevertheless, there is still uncertainty regarding its precise pharmacology, side effects, and toxicity, particularly in terms of its impact on organelle homeostasis. Here, we demonstrate that in budding yeast, HU specifically inhibits the endoplasmic reticulum–associated degradation (ERAD) of luminal misfolded proteins (ERAD-L pathway), an effect that is independent of S-phase arrest. In contrast, HU did not affect the degradation of misfolded ER membrane proteins or the degradation of cytosolic proteins. The selective inhibition of ERAD-L by HU is likely attributable to the formation of disulfide bonds in cysteine residues in luminal substrates, which must be reduced before their retrotranslocation to the cytosol. We further demonstrate that HU plays a role in alleviating reductive stress phenotypes observed in cells lacking Ero1, which is essential for oxidative protein folding in the ER. We propose that HU functions as a modulator of thiol–disulfide homeostasis in the ER lumen. |
| 書誌情報 |
en : Life Science Alliance
巻 8,
号 8,
ページ数 15,
発行日 2025-06-20
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| 出版者 |
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出版者 |
Life Science Alliance |
| ISSN |
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収録物識別子タイプ |
EISSN |
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収録物識別子 |
2575-1077 |
| 出版者版DOI |
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関連タイプ |
isReplacedBy |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.26508/lsa.202503225 |
| 出版者版URI |
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関連タイプ |
isReplacedBy |
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識別子タイプ |
URI |
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関連識別子 |
https://www.life-science-alliance.org/content/8/8/e202503225 |
| 権利 |
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権利情報Resource |
https://creativecommons.org/licenses/by/4.0/ |
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権利情報 |
© 2025 Takano et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
| 著者版フラグ |
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出版タイプ |
NA |
| 助成情報 |
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助成機関名 |
Japan Society for the Promotion of Science (JSPS) |
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研究課題番号 |
19H02923 |
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研究課題番号URI |
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19H02923/ |
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研究課題名 |
ユビキチン修飾を介した炭素代謝系の環境応答機構の解明 |
| 助成情報 |
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助成機関名 |
Japan Society for the Promotion of Science (JSPS) |
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研究課題番号 |
23K26869 |
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研究課題番号URI |
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23K26869/ |
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研究課題名 |
微生物におけるユビキチン修飾を介した脂質代謝・エネルギー代謝のストレス応答機構 |
| 助成情報 |
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助成機関名 |
Japan Society for the Promotion of Science (JSPS) |
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研究課題番号 |
24H01906 |
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研究課題番号URI |
https://kaken.nii.ac.jp/grant/KAKENHI-PUBLICLY-24H01906/ |
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研究課題名 |
タンパク質半減期の網羅測定を軸とした細胞の栄養応答・適応機構の解析 |
| 助成情報 |
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助成機関名 |
Hori Sciences and Arts Foundation |
| 助成情報 |
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助成機関名 |
Institute for Fermentation, Osaka |
| 助成情報 |
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助成機関名 |
Japan Science and Technology Agency (JST) |
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研究課題番号 |
JPMJSP2130 |
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研究課題名 |
SPRING |
