The molecular mechanism of Hox gene regulation by leukemic fusion proteins
| Project/Area Number |
17H03679
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cell biology
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| Research Institution | National Institutes of Biomedical Innovation, Health and Nutrition |
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Principal Investigator |
Oka Masahiro 国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 細胞核輸送ダイナミクスプロジェクト, プロジェクトリーダー (40432504)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2019: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2017: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | CRM1 / ヌクレオポリン / 白血病 / HOX / 融合遺伝子 / 細胞核 / 遺伝子発現 / 核輸送因子 / 細胞・組織 / 融合遺伝子産物 / 遺伝子 / 癌 / ゲノム / 発現制御 |
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| Outline of Final Research Achievements |
The molecular mechanism of abnormal HOX (homeobox) gene expression in acute leukemia remains largely elusive. In this study, we found that leukemia-related proteins such as nucleoporin fusion proteins and mutant NPM1 are recruited to HOX cluster regions through their interaction with a nuclear export factor, CRM1, in human leukemia cell lines. Furthermore, our results showed that the transcriptional activation of HOX genes occurs in a CRM1-dependent manner in these cells.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、核―細胞質間分子輸送機構の異常と病態との関連が明らかになりつつある。本研究によって、核から細胞質への分子輸送に必須の核外輸送因子CRM1と核膜孔構成因子（ヌクレオポリン）との相互作用や、CRM1と核外移行シグナルとの相互作用が、白血病でみられるHOX遺伝子の発現異常にも深く関わっていることが明らかとなった。今後の新規治療薬の開発にもつながる成果であると考えられる。
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Report
(4 results)
Research Products
(31 results)
