Molecular analysis of the proteasome gene expression and its application to anti-aging.
| Project/Area Number |
16H03265
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied health science
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| Research Institution | Doshisha University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
和久 剛 同志社大学, 生命医科学部, 助教 (40613584)
依馬 正次 滋賀医科大学, 動物生命科学研究センター, 教授 (60359578)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2016: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
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| Keywords | タンパク質恒常性 / アンチエイジング / 老化 / 遺伝子発現 / プロテアソーム / タンパク質分解 / 転写 / 転写因子 |
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| Outline of Final Research Achievements |
Cells, which are small units of our body, has multiple regulatory systems to sustain its homeostasis. Protein homeostasis (i.e. proteostasis) is one of such regulatory mechanisms. We discovered that a transcription factor NRF1 (NFE2L1) regulates not only Proteasome that is a crucial proteolysis enzyme, but also Autophagy that is another protein degradation system. In addition, we found that NRF1-related transcription factor NRF3 (NFE2L3) regulates gene expression of POMP as protein chaperon, thereby activating 20S proteasome that degrades cellular proteins related to ageing.
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| Academic Significance and Societal Importance of the Research Achievements |
細胞のタンパク質品質管理に関わるタンパク質分解酵素プロテアソームが、どのように発現するのか？というメカニズムについては、これまで長く不明であった。今回の研究の学術的な意義は、（1）NRF1と呼ばれるタンパク質が制御し、さらにオートファジーにも関与すること、そして（2）関連因子NRF3も異なるタンパク質分解経路に関わることを発見したことにある。本研究成果の社会的意義は、この知見にもとづいてNRF1あるいはNRF3を活性化する方法を開発すれば、細胞の恒常性の維持によるアンチエイジング法につながる点にある。
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Report
(4 results)
Research Products
(49 results)
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[Journal Article] Possible roles of the transcription factor Nrf1 (NFE2L1) in neural homeostasis by regulating the gene expression of deubiquitinating enzymes.2017
Author(s)
Taniguchi, H., Okamuro, S., Kohji, M., Waku, T., Kubo, K., Hatanaka, A., Sun, Y., A M Chowdhury, AM A., Fukamizu, A., Kobayashi, A.
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Journal Title
Biochem Biophys Res Commun.
Volume: 484
Issue: 1
Pages: 176-183
DOI
Related Report
Peer Reviewed
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[Journal Article] USP15 stabilizes the transcription factor Nrf1 in the nucleus, promoting the proteasome gene expression.2016
Author(s)
Fukagai, K., Waku, T., Chowdhury, AM., Kubo, K., Matsumoto, M., Kato, H., Natsume, T., Tsuruta, F., Chiba, T., Taniguchi, H., Kobayashi, A.
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Journal Title
Biochem Biophys Res Commun.
Volume: 478
Issue: 1
Pages: 363-370
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Patent(Industrial Property Rights)] 抗がん剤2016
Inventor(s)
和久剛、小林聡、加藤裕紀、渡辺秀教
Industrial Property Rights Holder
和久剛、小林聡、加藤裕紀、渡辺秀教
Industrial Property Rights Type
特許
Industrial Property Number
2016-230449
Filing Date
2016-11-28
Related Report
