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eLife.71966.pdf | 1.93 MB | Adobe PDF | 見る/開く |
タイトル: | IRAK1-dependent Regnase-1-14-3-3 complex formation controls Regnase-1-mediated mRNA decay |
著者: | Akaki, Kotaro Ogata, Kosuke https://orcid.org/0000-0002-0634-3990 (unconfirmed) Yamauchi, Yuhei Iwai, Noriki Tse Ka Man Fabian, Hia Mochizuki, Atsushi Ishihama, Yasushi https://orcid.org/0000-0001-7714-203X (unconfirmed) Mino, Takashi https://orcid.org/0000-0002-9562-008X (unconfirmed) Takeuchi, Osamu https://orcid.org/0000-0002-1260-6232 (unconfirmed) |
著者名の別形: | 赤木, 宏太朗 小形, 公亮 山内, 悠平 岩井, 紀貴 チェカメン フェビエン, ヒヤ 望月, 敦史 石濱, 泰 三野, 享史 竹内, 理 |
キーワード: | Research Article Immunology and Inflammation Human Mouse |
発行日: | 2021 |
出版者: | eLife Sciences Publications, Ltd |
誌名: | eLife |
巻: | 10 |
論文番号: | e71966 |
抄録: | Regnase-1 is an endoribonuclease crucial for controlling inflammation by degrading mRNAs encoding cytokines and inflammatory mediators in mammals. However, it is unclear how Regnase-1-mediated mRNA decay is controlled in interleukin (IL)-1β- or Toll-like receptor (TLR) ligand-stimulated cells. Here, by analyzing the Regnase-1 interactome, we found that IL-1β or TLR stimulus dynamically induced the formation of Regnase-1-β-transducin repeat-containing protein (βTRCP) complex. Importantly, we also uncovered a novel interaction between Regnase-1 and 14-3-3 in both mouse and human cells. In IL-1R/TLR-stimulated cells, the Regnase-1-14-3-3 interaction is mediated by IRAK1 through a previously uncharacterized C-terminal structural domain. Phosphorylation of Regnase-1 at S494 and S513 is critical for Regnase-1-14-3-3 interaction, while a different set of phosphorylation sites of Regnase-1 is known to be required for the recognition by βTRCP and proteasome-mediated degradation. We found that Regnase-1-14-3-3 and Regnase-1-βTRCP interactions are not sequential events. Rather, 14-3-3 protects Regnase-1 from βTRCP-mediated degradation. On the other hand, 14-3-3 abolishes Regnase-1-mediated mRNA decay by inhibiting Regnase-1-mRNA association. In addition, nuclear-cytoplasmic shuttling of Regnase-1 is abrogated by 14-3-3 interaction. Taken together, the results suggest that a novel inflammation-induced interaction of 14-3-3 with Regnase-1 stabilizes inflammatory mRNAs by sequestering Regnase-1 in the cytoplasm to prevent mRNA recognition. |
記述: | 炎症が制御される新たなメカニズムの解明 --タンパク質「14-3-3」を介した新たなRegnase-1の抑制機序--. 京都大学プレスリリース. 2021-10-19. |
著作権等: | © 2021, Akaki et al. This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited. |
URI: | http://hdl.handle.net/2433/265530 |
DOI(出版社版): | 10.7554/eLife.71966 |
PubMed ID: | 34636324 |
関連リンク: | https://www.kyoto-u.ac.jp/ja/research-news/2021-10-19-2 |
出現コレクション: | 学術雑誌掲載論文等 |
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