| Project/Area Number |
12680623
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional biochemistry
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
SHIMA Hiroshi Hokkaido Univ., Inst. Genet. Med., Asso. Prof., 遺伝子病制御研究所, 助教授 (10196462)
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| Co-Investigator(Kenkyū-buntansha) |
TANUMA Nobuhiro Hokkaido Univ., Inst. Genet. Med., lnst., 遺伝子病制御研究所, 助手 (40333645)
KIKUCHI Kunimi Hokkaido Univ., Inst. Genet. Med., Prof., 遺伝子病制御研究所, 教授 (20006117)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2000: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Keywords | S6 / phosphorylation / kinase / phosphatase / PP1 / PP2A / calcineurin / tautomycetin / S6キナーゼ / 欠損マウス / トウトマイシン / 細胞増殖 / 癌化 / 翻訳 / がん化 / 細胞周期 / 免疫抑制 |
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| Research Abstract |
1. Regulation of translation by type 1 protein phosphatase (PP1 )
PP1 is thought to be involved in dephosphorylation and negative regulation of S6 protein. Two kinds of PP1 regulatory proteins (NIPP-1 and 1-4) were identified and characterized. NIPP-1 was shown to bind 4 kinds of PP1 catalytic subunits with similar affinity. Expression of NIPP-1 mRNA in rat hepatomas was analyzed and It was shown that its level was positively correlated with the malignant phenotype.
We have isolated a novel and the most potent PP1 inhibitory protein named as I-4. IC50 towards PP1 of is 0.2hM. The experiments based on deletion mutants showed that I-4 inhibits PP1 by covering catalytic site of PP1 catalytic subunit by binding with 3 domains.
2. S6 kinase deficient mouse
Based on the phenotype of S6 kinase deficient mouse, we reveled a novel isotope of S6K, S6K2. Development and analysis of S6K2 deficient mouse is currently, on going.
3. Regulation of translation by type 2A protein phosphatase (PP2A)
APP2A regulatory protein (I-2/PP2A) was isolated. The expression of I-2/PP2A mRNA was regulated up regulated at G1/S. Over-expression of I-2/PP2A suppressed the cell proliferation.
4. Mechanism of immunosuppressive drug
Although the target of immunosuppressive drug such as cyclosporinA and FK506 is identified as calcineurin, the assay method for calcineurin activity has not been established well. We established the efficient and accurate method for enzyme activity of calcineurin.
5. Cross-talk between translation and major signal cascades
We have identified novel negative regulator named as MKP-7 (for MAPK pathway) and PTP epsilon (for JAK-STAT) and cauterized the mode of action of these proteins.
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