Pathogenic mechanism of neurodegenerative diseases associated with dysfunction of ubiquitin ligase
| Project/Area Number |
15K21706
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Institution | Hiroshima University |
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Principal Investigator |
Kaneko Masayuki 広島大学, 医歯薬保健学研究院(医), 准教授 (10322827)
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| Co-Investigator(Kenkyū-buntansha) |
保住 功 岐阜薬科大学, 薬学部, 教授 (20242430)
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2016: ¥715,000 (Direct Cost: ¥550,000、Indirect Cost: ¥165,000)
Fiscal Year 2015: ¥2,665,000 (Direct Cost: ¥2,050,000、Indirect Cost: ¥615,000)
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| Keywords | ユビキチンリガーゼ / 神経変性疾患 / アルツハイマー病 / ライソゾーム / オートファジー / アミノ酸トランスポーター / 神経細胞 / ユビキチン化 / RNF182 / mTORC1 / CRISPR / ノックアウトマウス / ERAD |
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| Outline of Final Research Achievements |
We identified 37 transmembrane ubiquitin ligases. In this study, we focused on RNF182, which is upregulated in the brain of Alzheimer’s disease patients. RNF182 is expressed specifically in the central nervous system and more intensely in the hippocampus. RNF182 is mainly localized in late endosomes and lysosomes. We identified the lysosome membrane protein, LAPTM4A, as an interactor with RNF182. RNF182 processed K63-linked polyubiquitin chains on LAPTM4A and promoted interaction of LAPTM4A with amino acid transporter, LAT1. Consequently, RNF182 may induce mTOCR1 signaling that leads to inhibition of autophagy.
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Report
(3 results)
Research Products
(31 results)
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[Journal Article] Genome-wide identification and gene expression profiling of ubiquitin ligases for endoplasmic reticulum protein degradation2016
Author(s)
Kaneko M, Iwase I, Yamasaki Y, Takai T, Wu Y, Kanemoto S, Matsuhisa K, Asada R, Okuma Y, Watanabe T, Imaizumi K, Nomura Y.
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Journal Title
Scientific reports
Volume: 6
Issue: 1
Pages: 30955-30955
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Luman is involved in osteoclastogenesis through the regulation of DC-STAMP expression, stability and localization.2015
Author(s)
Kanemoto S, Kobayashi Y, Yamashita T, Miyamoto T, Cui M, Asada R, Cui X, Hino K, Kaneko M, Takai T, Matsuhisa K, Takahashi N, Imaizumi K.
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Journal Title
J Cell Sci
Volume: 128
Pages: 4353-4365
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Evaluation of synthetic naphthalene derivatives as novel chemical chaperones that mimic 4-phenylbutyric acid.2015
Author(s)
Mimori S, Koshikawa Y, Mashima Y, Mitsunaga K, Kawada K, Kaneko M, Okuma Y, Nomura Y, Murakami Y, Kanzaki T, Hamana H.
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Journal Title
Bioorg Med Chem Lett.
Volume: 25
Issue: 4
Pages: 811-814
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Involvement of Serotonin Transporter Gene Polymorphisms (5-HTT) in Impulsive Behavior in the Japanese Population2015
Author(s)
NOMURA, M., KANEKO, M., OKUMA, Y., NOMURA, J., KUSUMI, I., KOYAMA, T., NOMURA, Y
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Journal Title
PLoS One
Volume: 16
Issue: 3
Pages: 1-14
DOI
NAID
Related Report
Peer Reviewed / Open Access
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