| Project/Area Number |
15K09487
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
OKUDA Tsukasa 京都府立医科大学, 医学(系)研究科(研究院), 教授 (30291587)
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| Co-Investigator(Kenkyū-buntansha) |
吉田 達士 京都府立医科大学, 医学(系)研究科(研究院), 助教 (80315936)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 白血病 / 造血幹細胞 / リンパ球 / 転写因子 / 翻訳後修飾 / RUNX1 / AML1 / TRAIL / 造血器疾患 / 分子標的 / 染色体転座 / CBFB / 転写コファクター |
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| Outline of Final Research Achievements |
Runt-related transcription factor 1, RUNX1, is a frequent target of leukemia-related gene aberrations. Although a number of the transcriptional target genes have been so far identified, many should still remain to be elucidated. In this project, we identified that tumor-necrosis factor-related apoptosis-inducing ligand (TRAIL) is the novel transcriptional target of RUNX1. TRAIL is a secreted cytokine or a membrane-binding molecule that functions in anti-tumor effects. We found that RUNX1 up-regulated TRAIL promoter activity, detected by the luciferase reporter assay. In this promoter region, some possible RUNX1-binding consensus sequences were found, however, a site-directed mutagenesis revealed that none of them appeared to be responsible for the activation of TRAIL transcription by RUNX1. Further analyses revealed that the proximal region was responsible for this RUNX1 transcription activity, suggesting that RUNX1 regulates TRAIL transcription by a novel molecular mechanism.
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