Chemo-sensitivity profiling of changing p53 cellular localization
| Project/Area Number |
18590668
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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 |
Gastroenterology
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| Research Institution | Tohoku University |
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Principal Investigator |
KATO Shunsuke Tohoku University, Tohoku University Hospital, Lecturer (40312657)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,100,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥600,000)
Fiscal Year 2007: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | p53 / Doxycyclin inducible stable transformant / Chemo-sensitivity / Cellular localization / 抗がん剤感受性 / 安定発現形 |
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| Research Abstract |
After DNA damage, p53 is accumulated in nucleus and trans-activate downstream genes and induces cell cycle arrest and apoptosis. Previous studies have shown transactivation-dependent and independent pathways for p53-dependent apoptosis. Previously, S121F mutant was shown to have a strong ability to induce apoptosis (super p53). In the present study, we constructed p53-inducible-cell lines in P53-null SF126 glioblastoma cells and analyzed them for the induction of cell cycle arrest, apoptosis and transactivation of p53-downstream genes after nuclear or cytoplasmic expression of p53. R306G mutant was used to sequester p53 to the cytoplasm. Wild-type p53 retained the ability to arrest the cell cycle, and S121F retained a strong ability to induce apoptosis even when these were exclusively sequestered from the nucleus into the cytoplasm. Surprisingly, cytoplasmically sequestered wild-typed p53 and S121F could transactivate the downstream genes with distinct expression profiles, and the strong apoptotic ability of S121F was not associated with its transactivation activity. These results underscore the existence of transactivation-independent apoptosis and cytoplasmic function of p53.
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(3 results)
Research Products
(3 results)
