| Project/Area Number |
26460667
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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 |
Laboratory medicine
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| Research Institution | Chiba University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
野村 文夫 千葉大学, 医学部附属病院, 特任教授 (80164739)
星野 忠次 千葉大学, 大学院薬学研究院, 准教授 (90257220)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | T細胞性急性リンパ性白血病 / 質量分析 / モデルマウス / ｃ－ｍｙｃ / PKM2 / PUF60/FIR / 急性リンパ性白血病 / 癌糖代謝 / c-myc / スプライシング / 急性Tリンパ性白血病 / 転写因子 / Ｔ細胞性急性リンパ性白血病 / ｃ-ｍｙｃ遺伝子 / 臓器浸潤 / ノックアウトマウス / 機能解析 |
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| Outline of Final Research Achievements |
The switch of pyruvate kinase (PK) M1 and PKM2 is pivotal for glucose metabolism in cancers. FUSE-binding protein (FBP)-interacting repressor (FIR) is a transcriptional repressor of the c-myc gene. This study investigated the thymic lymphoma tissues of mice and revealed that haplodeficiency of FIR significantly contributed to the splicing of PKM1 to PKM2 in mice thymic lymphoma using six-plex tandem mass tag (TMT) quantitative proteomic analysis in this mice model. TMT revealed 648 proteins that were up- or downregulated in mice thymic lymphoma tissues. Among them, PKM2 protein, but not PKM1, was upregulated in the thymic lymphoma as well as T-ALL. These results indicated that FIR haplodeficiency contributes the alternative splicing of PKM1 to PKM2 by partly inhibiting hnRNPA1 expression in the thymic lymphoma cells prior to T-ALL. Taken together, our findings suggest that FIR and its related spliceosomes are potential therapeutic targets for cancers, including T-ALL.
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