| Project/Area Number |
12672144
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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 |
Biological pharmacy
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| Research Institution | SHOWA UNIVERSITY (2001)
The Institute of Physical and Chemical Research (2000) |
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Principal Investigator |
WATABE Masahiko School of Pharmaceutical Sciences Showa University Researcher, 薬学部, 助手 (90301788)
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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 |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2000: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Cell Division / Cell Growth / Cell Death / Protein Kinase / MST / Krsタンパク質 |
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| Research Abstract |
Staurosporine and its analogues (K-2S2a, RK-286C) are known to inhibit the protein kinases and also to cause DNA re-replication the same as cytochalasin B in rat diploid fibroblast 3Y1 cells without an intervening mitosis, producing tetraploid cells. We found that these drugs induced the increase of cell size by the inhibition of cell division but not nucleus division in human chronic myelogenous leukemia K562 cells. This phenomenon was expected to the relation of one protein kinase and we found that the human protein kinases, MST1/Krs2 and MST2/Kpsl, related to the cell division on the cell proliferation and might be one of the target factors of those drugs. To examine the importance of MST/Krs in the cell division, we investigated the effect of kinase-inactive MST/Krs expression during the cell proliferation. The expression of kinase-inactive MST/Krs in K562 cells induced the inhibition of cell growth and increase of the cell size was caused by the increase of nucleus count in the cells. Moreover, we performed the double staining with Hoechst 33258 and rhodamine phalloidin, when the kinase-inactive MST/KrS was overexpressed in human cervix epithelioid carcinoma HeLa cells. On the cells expressed kinase-inactive MST/Krs, we observed the increase of the nucleus count and the siassembly of actin filament. These results suggest that MST/Krs is one of the target factors of those drugs and plays the important role on the cell division by the relation to the stability of cytoskeleton protein such as actin.
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