Anti-aging drugs by targeting PTEN
Project/Area Number |
20K20661
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Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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Allocation Type | Multi-year Fund |
Review Section |
Studies on the Super-Aging Society
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Research Institution | Kobe University |
Principal Investigator |
Suzuki Akira 神戸大学, 医学研究科, 教授 (10311565)
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Project Period (FY) |
2020-07-30 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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Keywords | PTEN / 長寿薬 / がん抑制遺伝子 / 長寿 |
Outline of Research at the Start |
健康的に長寿を迎えたいという欲求は、古来からの人間の根源的な欲望である。 近年、線虫やショウジョウバエにおいて、寿命を制御する遺伝子がいくつか判明し、抗糖尿病薬メトフォルミンを投与した正常マウスが長寿になること等も示されて、人類が古来から夢見ていた長寿薬の探索が現実となってきた。 今回我々はPTENの不安定化分子を標的とする長寿薬のハイスループットスクリーニングを行い、健康的寿命の延長と国民福祉の向上を目指す。
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Outline of Final Research Achievements |
Two E3 SUMOylating enzymes (X, Y) and the deubiquitinating enzyme Z were identified as PTEN binding and destabilising molecules. Knockdown of X and Y increased PTEN, decreased phosphorylated AKT and reduced cell proliferation, whereas knockdown of Z resulted in nuclear localisation of PTEN and increased PTEN protein. X and Y homozygous deletion mice have been generated and their longevity is currently being investigated. On the other hand, we found that WWP2, one of the 5 PTEN E3 ligases, has the highest PTEN destabilising effect, so a PTEN-WWP2 binding visualisation system was established and chemical compounds were screened. Six compounds were positive, but no PTEN increase was obtained. We are currently screening for unpublished small molecules.
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Academic Significance and Societal Importance of the Research Achievements |
長寿薬の開発は古来からの人類の夢であり、その開発が待たれる。近年PTENを軽度増加せると寿命が延長することが示された。一方PTENは代表的な癌抑制ドライバー分子であるために、その制御機構の解明は癌治療につながる。本研究によって癌の発症抑制をも兼ねそなえた、PTENタンパク質安定性亢進を標的とする長寿薬の開発によって、健康寿命の延長と国民福祉の向上を狙うことが可能となる。
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Report
(4 results)
Research Products
(38 results)
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[Journal Article] A mass spectrometric method for in-depth profiling of phosphoinositide regioisomers and their diseaseassociated regulation.2022
Author(s)
Morioka S, Nakanishi H, Yamamoto T, Hasegawa J, Tokuda E, Hikita T, Sakihara T, Kugii Y, Oneyama C, Yamazaki M, Suzuki A, Sasaki J, Sasaki T.
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Journal Title
Nature Communications
Volume: 13(1)
Issue: 1
Pages: 83-83
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Alantolactone is a natural product that potently inhibits YAP1/TAZ through promotion of reactive oxygen species accumulation.2021
Author(s)
Nakatani K, Maehama T, Nishio M, Otani J, Yamaguchi K, Fukumoto M, Hikasa H, Hagiwara S, Nishina H, Mak TW, Honma T, Kondoh Y, Osada H, Yoshida M, Suzuki A
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Journal Title
Cancer Science
Volume: 112
Issue: 10
Pages: 4303-4316
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Prostaglandin E2 and its receptor EP2 trigger signaling that contributes to YAP-mediated cell competition.2020
Author(s)
Ishihara E, Nagaoka Y, Okuno T, Kofuji S, Ishigami-Yuasa M, Kagechika H, Kamimura K, Terai S, Yokomizo T, Sugimoto Y, Fujita Y, Suzuki A, Nishina H.
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Journal Title
Genes Cells.
Volume: 25(3)
Issue: 3
Pages: 197-214
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Endogenous YAP1 activation drives immediate onset of cervical carcinoma in situ in mice.2020
Author(s)
Miki Nishio , Yoko To , Tomohiko Maehama , Yukari Aono , Junji Otani , Hiroki Hikasa , Akihiro Kitagawa , Koshi Mimori , Takehiko Sasaki , Hiroshi Nishina , Shinya Toyokuni , John P Lydon , Kazuwa Nakao , Tak Wah Mak , Tohru Kiyono , Hidetaka Katabuchi , Hironori Tashiro , Akira Suzuki
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Journal Title
Cancer science
Volume: 111
Issue: 10
Pages: 3576-3578
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Book] 医学のあゆみ2020
Author(s)
前濱 朝彦、西尾 美希、鈴木 聡
Total Pages
5
Publisher
医歯薬出版株式会社
Related Report