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G3BP1 inhibits ubiquitinated protein aggregations induced by p62 and USP10
http://hdl.handle.net/10191/00051722
http://hdl.handle.net/10191/0005172255050e2e-7a20-482f-9505-b7918988908b
名前 / ファイル | ライセンス | アクション |
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本文 (9.8 MB)
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要旨 (681.3 kB)
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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公開日 | 2020-07-08 | |||||
タイトル | ||||||
タイトル | G3BP1 inhibits ubiquitinated protein aggregations induced by p62 and USP10 | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源 | http://purl.org/coar/resource_type/c_46ec | |||||
タイプ | thesis | |||||
その他のタイトル | ||||||
その他のタイトル | G3BP1はp62とUSP10によるユビキチン化蛋白質の凝集体形成を抑制する | |||||
著者 |
Anisimov, Sergei
× Anisimov, Sergei |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | The aberrant accumulation of ubiquitinated protein aggregates in cells plays a critical role in the pathogenesis of several degenerative diseases, including Parkinson disease (PD) and cystic fibrosis (CF). In this study, we found that Ras GTPase-activating protein-binding protein 1 (G3BP1) inhibits ubiquitinated protein aggregations induced by p62 and USP10 in cultured cells. p62 is a ubiquitin receptor, and p62 and its binding partner USP10 have been shown to augment ubiquitinated protein aggregation. G3BP1 interacted with p62 and USP10 and inhibited p62/USP10-induced protein aggregation. The G3BP1 inhibition of protein aggregations targeted two aggregation-prone proteins, α-synuclein and CFTR-∆F508, which are causative factors of PD and CF, respectively. G3BP1 depletion increased the amounts of ubiquitinated α-synuclein and CFTR-∆F508 protein. A proteasome reporter indicated that G3BP1 depletion inhibits the proteasome activity. We herein present evidence that G3BP1, p62 and USP10 together control ubiquitinated protein toxicity by controlling both ubiquitination and aggregation. Taken together, these results suggest that G3BP1, p62 and USP10 could be therapeutic targets for ubiquitinated protein aggregation disorders, including PD and CF. | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Scientific Reports. 2019, 9(1), 12896 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | info:doi/10.1038/s41598-019-46237-1 | |||||
著者版フラグ | ||||||
値 | ETD | |||||
学位名 | ||||||
学位名 | 博士(医学) | |||||
学位授与機関 | ||||||
学位授与機関名 | 新潟大学 | |||||
学位授与年月日 | ||||||
学位授与年月日 | 2019-09-20 | |||||
学位授与番号 | ||||||
学位授与番号 | 13101甲第4641号 | |||||
学位記番号 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 新大院博(医)甲第901号 |