| Item type |
文献 / Documents(1) |
| 公開日 |
2021-01-29 |
| アクセス権 |
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アクセス権 |
open access |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| 出版社版DOI |
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関連識別子 |
https://doi.org/10.1096/fj.15-275990 |
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関連名称 |
10.1096/fj.15-275990 |
| 出版タイプ |
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出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
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|
タイトル |
Skeletal muscle‐specific eukaryotic translation initiation factor 2α phosphorylation controls amino acid metabolism and fibroblast growth factor 21‐mediated non‐cell‐autonomous energy metabolism |
| タイトル別表記 |
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その他のタイトル |
ISR-DEPENDENT METABOLIC REGULATION |
| 著者 |
三宅, 雅人
ノムラ, アキトシ
小倉, 淳
タケハナ, ケンジ
キタハラ, ヨシヒロ
髙原, 一菜
ツガワ, カズエ
ミヤモト, チノブ
ミウラ, ナオコ
佐藤, 亮祐
倉橋, 清衛
Harding, Heather P.
親泊, 美帆
Ron, David
親泊, 政一
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| 抄録 |
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内容記述 |
The eukaryotic translation initiation factor 2α (eIF2α) phosphorylation‐dependent integrated stress response (ISR), a component of the unfolded protein response, has long been known to regulate intermediary metabolism, but the details are poorly worked out. We report that profiling of mRNAs of transgenic mice harboring a ligand‐activated skeletal muscle–specific derivative of the eIF2α protein kinase R‐like ER kinase revealed the expected up‐regulation of genes involved in amino acid biosynthesis and transport but also uncovered the induced expression and secretion of a myokine, fibroblast growth factor 21 (FGF21), that stimulates energy consumption and prevents obesity. The link between the ISR and FGF21 expression was further reinforced by the identification of a small‐molecule ISR activator that promoted Fgf21 expression in cell‐based screens and by implication of the ISR‐inducible activating transcription factor 4 in the process. Our findings establish that eIF2α phosphorylation regulates not only cell‐autonomous proteostasis and amino acid metabolism, but also affects non‐cell‐autonomous metabolic regulation by induced expression of a potent myokine.—Miyake, M., Nomura, A., Ogura, A., Takehana, K., Kitahara, Y., Takahara, K., Tsugawa, K., Miyamoto, C., Miura, N., Sato, R., Kurahashi, K., Harding, H. P., Oyadomari, M., Ron, D., Oyadomari, S. Skeletal muscle‐specific eukaryotic translation initiation factor 2α phosphorylation controls amino acid metabolism and fibroblast growth factor 21‐mediated non‐cell‐autonomous energy metabolism. |
| キーワード |
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|
主題 |
ER stress |
| キーワード |
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主題 |
ATF4 |
| キーワード |
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主題 |
glutathione |
| キーワード |
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主題 |
obesity |
| キーワード |
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主題 |
small molecule |
| 書誌情報 |
en : The FASEB Journal
巻 30,
号 2,
p. 798-812,
発行日 2015-10-20
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| 収録物ID |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
15306860 |
| 収録物ID |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
08926638 |
| 収録物ID |
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収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA1066874X |
| 収録物ID |
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収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA12037502 |
| 出版者 |
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出版者 |
Federation of American Societies for Experimental Biology |
| 出版者 |
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出版者 |
John Wiley & Sons |
| 権利情報 |
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|
権利情報 |
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| EID |
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識別子 |
311188 |
| 言語 |
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言語 |
eng |
faseb_30_2_798.pdf (1.42 MB)
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