| Project/Area Number |
26650011
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Molecular biology
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Ito Akihiro 国立研究開発法人理化学研究所, 吉田化学遺伝学研究室, 専任研究員 (40391859)
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| Co-Investigator(Renkei-kenkyūsha) |
Moto Kenichi 国立研究開発法人理化学研究所, 小林脂質生物学研究室, 専任研究員 (90333335)
Kudo Norio 国立研究開発法人理化学研究所, 環境資源科学研究センター, 研究員 (80632421)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | Sirtuin / 代謝物質 / アセチル化 / SIRT2 / サーチュイン |
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| Outline of Final Research Achievements |
Sirtuins possess NAD-dependent deacetylase activity and is involved in diverse biological processes including aging. The enzymatic activity of sirtuins is known to be regulated by cellular NAD/NADH ratio. However, endogenous inhibitors for sirtuins have not been identified yet. Here, we identified N-acyldopamines as endogenous SIRT2 inhibitors. We found that a number of N-acyldopamine species including N-palmitoyldopamine inhibit both in vitro and in vivo SIRT2 activity. In addition, X-ray crystallographic analysis of the SIRT2―N-palmitoyldopamine complex revealed the molecular mechanism by which N-acyldopamines inhibit the SIRT2 activity.
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