Trib1 is an important adaptor that connects the MAP kinase pathway with C/EBPa in leukemogenesis
| Project/Area Number |
25430121
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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 |
Tumor biology
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| Research Institution | Japanese Foundation for Cancer Research |
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Principal Investigator |
Yokoyama Takashi 公益財団法人がん研究会, 発がん研究部, 研究員 (00535833)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | Trib1 / C/EBPα / Hoxa9 / Bcl11a / 白血病 / ノックアウトマウス / ChIPシークエンス / 転写因子 / レトロウィルス挿入変異 / レトロウイルス挿入変異 / MAPキナーゼ経路 |
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| Outline of Final Research Achievements |
Trib1 is a collaborator of Hoxa9/Meis1 in AML and it by itself induces AML through enhancement of MAP kinase signaling and degradation of C/EBPa. Biological phenotypes of Hoxa9-immortalized cells with different Trib1 expression status, Trib1 hi, Trib1 lo and Trib1 null, were compared. Proliferation, DNA synthesis and pERK was increased in the Trib1 hi cell. Genome-wide DNA-binding region of Hoxa9 and C/EBPa were then assessed in Trib1 hi, Trib1 lo and Trib1 null and potentially important Hoxa9 and C/EBPa target genes were searched in nearest neighbor genes of their binding peaks of which expression was 1.5-fold up- or down-regulated by Trib1 overexpression. Cdk6, Kit, Cd44, and Cd34 are such Hoxa9 target candidates up-regulated by Trib1. Also, Idh1, Tet2 and Vcam1 are down-regulated genes. These results suggested that Trib1 might alter cell cycle progression and differentiation by modulating Hoxa9-mediated transcriptional program and by repressing C/EBPa target tumor suppressor genes.
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Report
(4 results)
Research Products
(11 results)
