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The CCR4-NOT deadenylase complex controls Atg7-dependent cell death and heart function
https://oist.repo.nii.ac.jp/records/730
https://oist.repo.nii.ac.jp/records/730ee6b29d2-ac21-45fd-8c72-74d51c99f4cb
名前 / ファイル | ライセンス | アクション |
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Yamaguchi_et_al_2018 (5.9 MB)
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Science Journals Default License
(http://www.sciencemag.org/about/science-licenses-journal-article-reuse?_ga=2.2631088.1604802193.1540956321-1973906579.1540956321) |
Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2018-10-23 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | The CCR4-NOT deadenylase complex controls Atg7-dependent cell death and heart function | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | 著者最終版 共著者同意済み | |||||
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 | |||||
著者(英) |
Yamaguchi, Tomokazu
× Yamaguchi, Tomokazu× Suzuki, Takashi× Sato, Teruki× Takahashi, Akinori× Watanabe, Hiroyuki× Kadowaki, Ayumi× Natsui, Miyuki× Inagaki, Hideaki× Arakawa, Satoko× Nakaoka, Shinji× Koizumi, Yukio× Seki, Shinsuke× Adachi, Shungo× Fukao, Akira× Fujiwara, Toshinobu× Natsume, Tohru× Kimura, Akinori× Komatsu, Masaaki× Shimizu, Shigeomi× Ito, Hiroshi× Suzuki, Yutaka× Penninger, Josef M.× Yamamoto, Tadashi× Imai, Yumiko× Kuba, Keiji |
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書誌情報 |
en : Science Signaling 巻 11, 号 516, p. eaan3638, 発行日 2018-02-06 |
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抄録 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Shortening and removal of the polyadenylate [poly(A)] tail of mRNA, a process called deadenylation, is a key step in mRNA decay that is mediated through the CCR4-NOT (carbon catabolite repression 4-negative on TATA-less) complex. In our investigation of the regulation of mRNA deadenylation in the heart, we found that this complex was required to prevent cell death. Conditional deletion of the CCR4-NOT complex components Cnot1 or Cnot3 resulted in the formation of autophagic vacuoles and cardiomyocyte death, leading to lethal heart failure accompanied by long QT intervals. Cnot3 bound to and shortened the poly(A) tail of the mRNA encoding the key autophagy regulator Atg7. In Cnot3-depleted hearts, Atg7 expression was posttranscriptionally increased. Genetic ablation of Atg7, but not Atg5, increased survival and partially restored cardiac function of Cnot1 or Cnot3 knockout mice. We further showed that in Cnot3-depleted hearts, Atg7 interacted with p53 and modulated p53 activity to induce the expression of genes encoding cell death-promoting factors in cardiomyocytes, indicating that defects in deadenylation in the heart aberrantly activated Atg7 and p53 to promote cell death. Thus, mRNA deadenylation mediated by the CCR4-NOT complex is crucial to prevent Atg7-induced cell death and heart failure, suggesting a role for mRNA deadenylation in targeting autophagy genes to maintain normal cardiac homeostasis. | |||||
出版者 | ||||||
出版者 | Science Signaling | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 1937-9145 | |||||
PubMed番号 | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | PMID | |||||
関連識別子 | info:pmid/29438013 | |||||
DOI | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | DOI | |||||
関連識別子 | info:doi/10.1126/scisignal.aan3638 | |||||
権利 | ||||||
権利情報 | © 2018 The Author(s). | |||||
権利 | ||||||
権利情報 | This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science Signaling on Vol. 11, Issue 516, 06 Feb 2018, DOI: 10.1126/scisignal.aan3638. | |||||
関連サイト | ||||||
識別子タイプ | URI | |||||
関連識別子 | http://stke.sciencemag.org/content/11/516/eaan3638 | |||||
著者版フラグ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa |