| Project/Area Number |
14380299
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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 |
Functional biochemistry
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
KIKUCHI Kunimi HOKKAIDO UNIV., INST.GENETIC MED., PROF., 遺伝子病制御研究所, 教授 (20006117)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMA Hiroshi MIYAGI CANCER CENT.RES.INST., CHIEF, 研究所, 部長 (10196462)
TANUMA Nobuhiro HOKKAIDO UNIV., INST.GENETIC MED., INST., 遺伝子病制御研究所, 助手 (40333645)
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| Project Period (FY) |
2002 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2003: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 2002: ¥6,200,000 (Direct Cost: ¥6,200,000)
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| Keywords | PP1 / NIPP-1 / PTPεC / MKP-7 / LDP-3 / Raf-1 / siRNA / JNK / トウトマイセチン / DSP / B-Raf / インヒビター2 / Raf / JNKホスファターゼ / トートマイセチン / ERK / M1細胞 / ストレス応答 / LDP / プロテインホスファターゼ |
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| Research Abstract |
1.Using tautomycetin, a novel inhibitor of PP1, we found that PP1 activates Raf-1, resulting in activation of the ERK pathway.
2.Expression of C-terminal region-deleted mutant of NIPP1 (NIPP-1-ΔC) induced arrest of the cell cycle and apoptosis. In experiments with a reporter gene, NIPP1-ΔC suppressed splicing of pre-mRNA and decreased level of matured mRNA.
3.The PP1α-depleted HeLa cells rounded up and showed increased cell death, indicating that PP1α is essential for cell proliferation.
4.Scid and nude mice inoculated with PTPεC-expresser-M1 cells (M1εC) showed significantly prolonged survival time compared with parent M 1 cells.
5.Serine-446 in the C-terminal stretch of MKP-7, a novel JNK phosphatase, can be phosphorylated by activated ERK. This phosphorylation stabilized MKP-7 from ubiquitine-dependent degradation. These results strongly suggest that activation of the ERK pathway blocks JNK activation through stabilization of MKP-7 by phosphorylation.
6.Forced expression of a novel DSP,LDP-3, in COS-7 cells rathor enhanced activation of JNK and p38.
These results demonstrate crucial involvement of protein phosphatases in signal transduction under various conditions including cell proliferation, the cell cycle, cancer, apoptosis, and stress.
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