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UBL3 interacts with alpha-synuclein in cells and the interaction is downregulated by the EGFR pathway inhibitor osimertinib
http://hdl.handle.net/10271/0002000200
http://hdl.handle.net/10271/0002000200ae0a3157-7475-4c7b-b97e-78419ccf951a
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
論文本文 (2.7 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||
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| 公開日 | 2024-09-04 | |||||||||
| タイトル | ||||||||||
| タイトル | UBL3 interacts with alpha-synuclein in cells and the interaction is downregulated by the EGFR pathway inhibitor osimertinib | |||||||||
| 言語 | en | |||||||||
| 言語 | ||||||||||
| 言語 | eng | |||||||||
| キーワード | ||||||||||
| 主題 | UBL3 | |||||||||
| キーワード | ||||||||||
| 主題 | α-synuclein | |||||||||
| キーワード | ||||||||||
| 主題 | interaction | |||||||||
| キーワード | ||||||||||
| 主題 | drug screen | |||||||||
| キーワード | ||||||||||
| 主題 | EGFR pathway inhibitor | |||||||||
| キーワード | ||||||||||
| 主題 | osimertinib | |||||||||
| キーワード | ||||||||||
| 主題 | downregulate | |||||||||
| キーワード | ||||||||||
| 主題 | α-synucleinopathies | |||||||||
| 資源タイプ | ||||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||||
| 資源タイプ | doctoral thesis | |||||||||
| アクセス権 | ||||||||||
| アクセス権 | open access | |||||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||
| その他のタイトル | ||||||||||
| その他のタイトル | UBL3は細胞内でα-シヌクレインと相互作用し、その相互作用はEGFR経路阻害剤オシメルチニブによってダウンレギュレーションされる | |||||||||
| 著者 |
Chen, Bin
× Chen, Bin
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| 書誌情報 |
en : Biomedicines 巻 11, 号 6, p. 1685, ページ数 16, 発行日 2023-06-10 |
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| 出版者 | ||||||||||
| 出版者 | MDPI | |||||||||
| 言語 | en | |||||||||
| 権利 | ||||||||||
| 言語 | en | |||||||||
| 権利情報 | (C) 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). | |||||||||
| 抄録 | ||||||||||
| 内容記述タイプ | Abstract | |||||||||
| 内容記述 | Ubiquitin-like 3 (UBL3) acts as a post-translational modification (PTM) factor and regulates protein sorting into small extracellular vesicles (sEVs). sEVs have been reported as vectors for the pathology propagation of neurodegenerative diseases, such as α-synucleinopathies. Alpha-synuclein (α-syn) has been widely studied for its involvement in α-synucleinopathies. However, it is still unknown whether UBL3 interacts with α-syn, and is influenced by drugs or compounds. In this study, we investigated the interaction between UBL3 and α-syn, and any ensuing possible functional and pathological implications. We found that UBL3 can interact with α-syn by the Gaussia princeps based split luciferase complementation assay in cells and immunoprecipitation, while cysteine residues at its C-terminal, which are considered important as PTM factors for UBL3, were not essential for the interaction. The interaction was upregulated by 1-methyl-4-phenylpyridinium exposure. In drug screen results, the interaction was significantly downregulated by the treatment of osimertinib. These results suggest that UBL3 interacts with α-syn in cells and is significantly downregulated by epidermal growth factor receptor (EGFR) pathway inhibitor osimertinib. Therefore, the UBL3 pathway may be a new therapeutic target for α-synucleinopathies in the future. | |||||||||
| 言語 | en | |||||||||
| 学位名 | ||||||||||
| 学位名 | 博士（医学） | |||||||||
| 学位の区分 | ||||||||||
| 内容記述 | doctoral | |||||||||
| 学位の分野 | ||||||||||
| 内容記述 | 医学系研究科 | |||||||||
| 学位授与機関 | ||||||||||
| 学位授与機関識別子Scheme | kakenhi | |||||||||
| 学位授与機関識別子 | 13802 | |||||||||
| 学位授与機関名 | 浜松医科大学 | |||||||||
| 学位授与年月日 | ||||||||||
| 学位授与年月日 | 2023-09-22 | |||||||||
| 学位授与番号 | ||||||||||
| 学位授与番号 | 甲第952号 | |||||||||
| EISSN | ||||||||||
| 収録物識別子タイプ | EISSN | |||||||||
| 収録物識別子 | 2227-9059 | |||||||||
| PubMed番号 | ||||||||||
| 関連タイプ | isIdenticalTo | |||||||||
| 識別子タイプ | PMID | |||||||||
| 関連識別子 | 37371780 | |||||||||
| 出版社DOI | ||||||||||
| 関連タイプ | isIdenticalTo | |||||||||
| 識別子タイプ | DOI | |||||||||
| 関連識別子 | https://doi.org/10.3390/biomedicines11061685 | |||||||||
| 著者版フラグ | ||||||||||
| 出版タイプ | VoR | |||||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||
