| Project/Area Number |
16380225
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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 molecular and cellular biology
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| Research Institution | Tohoku University |
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Principal Investigator |
UCHIDA Takafumi Tohoku University, Tohoku University, Graduate School of Agricultural Scinece, Professor (80312239)
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| Co-Investigator(Kenkyū-buntansha) |
UCHIDA Chiyoko Ibaraki University, Health Center, Associate Professor (80312776)
RYONG-WOON Shin Tohoku University, Graduate School of Medicine, Associate Professor (40271910)
秋山 弘匡 東北大学, 学際科学国際高等研究センター, 講師 (40400254)
福本 学 東北大学, 加齢医学研究所, 教授 (60156809)
西森 克彦 東北大学, 大学院・農学系研究科, 教授
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| Project Period (FY) |
2004 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥16,460,000 (Direct Cost: ¥15,500,000、Indirect Cost: ¥960,000)
Fiscal Year 2007: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2006: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2005: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2004: ¥4,800,000 (Direct Cost: ¥4,800,000)
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| Keywords | peptidyl prolyl cis / trans isomerase / Pin1 / Myc / p53 / Amyloid / Notch1 / thymus / Alzheimer''s disease / mcl1 / プロテオーム / tat-Pin1 / リン酸化 / 癌 / 胸腺肥大 / ノックアウトマウス / プルセニリン / リチウム / Tau |
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| Research Abstract |
We found that. Pin1 is a stress resistance protein that is related to cancer and Alzheimer's disease. Pin1 regulates the stability of an oncogene, c-myc. C-myc is degraded by ubiquitination. If myc is not degraded and remains in the cell, the cell becomes immortalized and develops to cancer cell. Therefore Pin1 functions to resist to the stress of tumor development. The mice without Pin1 and p53 developed thymoma, which is caused by over production of NIC, activated Notch1. Pin1 also suppresses the tumor signal of Notch1. In brains, Pin1 regulate the production of Amyloid beta from amyloid precursor protein. Pin1 binds to the phosphoThr668 and changes the conformation of the site cut by g-secretase. Production of amyloid beta is considered one of the most important events in the development of Alzheimer's disease. Our finding will be useful to diagnose and produce a drug for Alzheimer's disease. We also discovered that Pin1 activates Stat3 signal, which is related to inflammation and immunity. This is the other example showing that. Pint is a responder to the stress to the cell or body. We also found that. Pin1 suppresses the apoptosis caused by spinal cord injury. We guessed there are molecules that function like Pin1 in the body to suppress. The stress, and found Gas7 that has similar amino acid sequence to Pin T. The level of Gas7 is very low in the brains of the patients with Alzheimer's disease. We think Gas7 may be another stress responsive protein like Pin1.
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