2022 Fiscal Year Final Research Report
Elucidation of the autophagy pathway associated with hyperosmotic-induced ubiquitin ligase RNF183
| Project/Area Number |
21K15271
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 47040:Pharmacology-related
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| Research Institution | Nagasaki University |
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Principal Investigator |
Okamoto Takumi 長崎大学, 医歯薬学総合研究科(薬学系), 特別研究員 (40826351)
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| Project Period (FY) |
2021-04-01 – 2023-03-31
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| Keywords | ユビキチンリガーゼ / RNF183 / 高浸透圧ストレス / NKCC1 / ビオチンリガーゼ |
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| Outline of Final Research Achievements |
The hyperosmotic-induced ubiquitin ligase RNF183 promotes the lysosomal degradation of ion transporters such as Na,K-ATPase and NKCC1 which were recognized as substrates by RNF183. There was a possibility that their degradation may be related to autophagy. However, when autophagy-related molecules ATG5 or Beclin1 were knocked out, no inhibition of their degradation was observed. This suggests that the degradation of ion transporters by RNF183 is a mechanism different from autophagy or a new degradation mechanism that is ATG5- and Beclin1-independent. We are also in the process of identifying the substrate proteins of RNF183 at the tissue level.
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| Free Research Field |
生化学・分子細胞生物学
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| Academic Significance and Societal Importance of the Research Achievements |
RNF183が発現する細胞によってその細胞への影響が異なる可能性を示せた。これは、本来腎臓特異的に発現しているRNF183が、炎症性腸疾患患者の大腸において異常発現している報告があることからも、腎臓ではRNF183の発現が細胞保護の働きを、その他の細胞においては細胞死への誘導作用がある可能性を示した。これより、RNF183が炎症性腸疾患の新たな治療ターゲットとなる可能性がある。また、マウスの組織レベルでのユビキチンリガーゼの基質タンパク質の同定を行っており、成功すれば、様々なタンパク質の生理条件下での機能解析への貢献が期待できる。
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