| Project/Area Number |
16K15386
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Hygiene and public health
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| Research Institution | National Institute for Environmental Studies |
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Principal Investigator |
Hirano Seishiro 国立研究開発法人国立環境研究所, 環境リスク・健康研究センター, 副研究センター長 (20150162)
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| Project Period (FY) |
2016-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2016: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
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| Keywords | ヒ素 / 細胞 / 前骨髄性白血病 / SUMO / 毒性 / PML / 白血病 |
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| Outline of Final Research Achievements |
SUMOylation of PML and tumor suppression events occur in response to arsenite (As3+). The solubility change of death-associated protein 6 (Daxx) and p53 repressor murine double minute 2 (MDM2) as well as PML and SUMO molecules in genetically engineered HEK293, Jurkat, and HL60 cells. PML and Daxx colocalized completely in immunofluorescence microscopic observation. However, Daxx was recovered in the RIPA-soluble fraction irrespective of exposure to As3+. MDM2, which is reportedly associated with PML in response to As3+, was also recovered in the RIPA-soluble fraction regardless of exposure to As3+. Those results indicate that proteins in the PML-NBs are subdivided at least into two compartments regarding the As3+-induced solubility change. An ancillary but significant finding was that MDM2-knockout cells were more resistant to As3+ than pristine cells. Although As3+ increased caspase-3/7 activity caspase inhibitors did not reduce the cytotoxic effects of As3+.
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