| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Research Abstract |
The purpose of this study is elucidation of the mechanism of PML NB foromation that is important for PML to exert its function. We investigated the mechanism of PML NB disruption by oncoprotein and the mechanism of PML NB restoration by arsenic trioxide (ATO), anti-tumor durg. PAX5-PML is the fist PML-fusion gene discovered other than PML-RARα. We demonstrated that PAX5-PML inhibited PML sumoylation, disrupted PML NB, and conferred apoptosis resistance on cells. Furthermore, treatment with arsenic trioxide induced PML sumoylation and reconstitution of PML NBs, and overcame the anti-apoptotic effect of PAX5-PML in cells. These data shed light to the mechanism of PML NB disruption and indicated that ATO targeted PML portion of PML fusion protein.
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