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GSK-3β-dependent downregulation of γ-taxilin and αNAC merge to regulate ER stress responses

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タイトル: GSK-3β-dependent downregulation of γ-taxilin and αNAC merge to regulate ER stress responses
著者: Hotokezaka, Yuka / Katayama, Ikuo / van Leyen, Klaus / Nakamura, Takashi
発行日: 2015年 4月16日
出版者: Nature Publishing Group
引用: Cell Death and Disease, 6(4), e1719; 2016
抄録: The signaling pathway leading to the endoplasmic reticulum (ER) stress responses has not been fully elucidated. Here we showed that glycogen synthase kinase-3β (GSK-3β)-dependent downregulation of γ-taxilin and nascent polypeptide-associated complex α-subunit (αNAC) mediates hypoxia-induced unfolded protein responses (UPRs) and the subsequent apoptotic and autophagic pathways. The degradation of γ-taxilin or αNAC was sufficient to initiate UPRs in normoxic cells. However, the ER stress signaling pathways initiated by γ-taxilin or αNAC were distinct, triggering different ER stress sensors and activating different downstream pathways. Hypoxia caused GSK-3β-dependent tau hyperphosphorylation and cleavage in neuronal cells, but γ-taxilin ablation induced tau hyperphosphorylation alone and αNAC ablation induced neither changes. Notably, downregulation of γ-taxilin and αNAC occurs in the brain of patients with Alzheimer's disease. These results suggest that GSK-3β-dependent downregulation of γ-taxilin and αNAC, which differently activate the UPRs, merge to regulate hypoxia-induced ER stress responses and provide a new insight into the pathogenesis of neurodegenerative diseases.
URI: http://hdl.handle.net/10069/37339
DOI: 10.1038/cddis.2015.90
権利: © 2015 Macmillan Publishers Limited. / This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
資料タイプ: Journal Article
原稿種類: publisher
出現コレクション:040 学術雑誌論文

引用URI : http://hdl.handle.net/10069/37339



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