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タイトル: | Unfolded protein response transducer IRE1-mediated signaling independent of XBP1 mRNA splicing is not required for growth and development of medaka fish |
著者: | Ishikawa, Tokiro https://orcid.org/0000-0003-1718-6764 (unconfirmed) Kashima, Makoto Nagano, Atsushi J Ishikawa-Fujiwara, Tomoko Kamei, Yasuhiro Todo, Takeshi Mori, Kazutoshi |
著者名の別形: | 森, 和俊 |
キーワード: | General Biochemistry, Genetics and Molecular Biology General Immunology and Microbiology General Neuroscience General Medicine |
発行日: | 27-Sep-2017 |
出版者: | eLife Sciences Organisation, Ltd. |
誌名: | eLife |
巻: | 6 |
論文番号: | e26845 |
抄録: | When activated by the accumulation of unfolded proteins in the endoplasmic reticulum, metazoan IRE1, the most evolutionarily conserved unfolded protein response (UPR) transducer, initiates unconventional splicing of XBP1 mRNA. Unspliced and spliced mRNA are translated to produce pXBP1(U) and pXBP1(S), respectively. pXBP1(S) functions as a potent transcription factor, whereas pXBP1(U) targets pXBP1(S) to degradation. In addition, activated IRE1 transmits two signaling outputs independent of XBP1, namely activation of the JNK pathway, which is initiated by binding of the adaptor TRAF2 to phosphorylated IRE1, and regulated IRE1-dependent decay (RIDD) of various mRNAs in a relatively nonspecific manner. Here, we conducted comprehensive and systematic genetic analyses of the IRE1-XBP1 branch of the UPR using medaka fish and found that the defects observed in XBP1-knockout or IRE1-knockout medaka were fully rescued by constitutive expression of pXBP1(S). Thus, the JNK and RIDD pathways are not required for the normal growth and development of medaka. The unfolded protein response sensor/transducer IRE1-mediated splicing of XBP1 mRNA encoding its active downstream transcription factor to maintain the homeostasis of the endoplasmic reticulum is sufficient for growth and development of medaka fish. |
著作権等: | © Ishikawa et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. |
URI: | http://hdl.handle.net/2433/227767 |
DOI(出版社版): | 10.7554/eLife.26845 |
PubMed ID: | 28952924 |
出現コレクション: | 学術雑誌掲載論文等 |
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