Role of tumor suppressor protein p53-inducible phosphatase PPM1D on neutrophil differentiation
| Project/Area Number |
17K17565
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Functional biochemistry
Cell biology
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| Research Institution | Hokkaido University |
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Principal Investigator |
Kamada Rui 北海道大学, 理学研究院, 助教 (40750881)
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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 |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 細胞分化 / ホスファターゼ / 阻害剤 / 好中球 / 発生・分化 / 細胞・組織 / タンパク質 / 免疫学 / 酵素 |
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| Outline of Final Research Achievements |
Tumor suppressor protein p53-inducible Ser/Thr phosphatase PPM1D has important role in DNA damage responses. Ppm1d knockout mice show multiple defects in immune responses and spermatogenesis. It is suggested that PPM1D plays an important role in immune cell differentiation and immune responses. In this study, we demonstrated that PPM1D inhibitor induced neutrophil differentiation of human promyelocytic leukemia cells. Furthermore, we showed that PPM1D regulates neutrophil immune function, such as phagocytosis. Using cell line which overexpressed PPM1D splice variants, PPM1D605 and PPM1D430, we clarified the role of PPM1D splice variants in neutrophil differentiation.
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| Academic Significance and Societal Importance of the Research Achievements |
免疫細胞への分化過程は遺伝子発現・制御因子の活性化により厳密に制御されており、分化の制御機構の破綻は、白血病や骨髄異形成症候群などの重篤な血液疾患を引き起こす。しかしながら、免疫細胞分化の分子制御機構はいまだ不明な点が多く、これら疾患の原因解明および新規治療法開発のために、免疫細胞分化および免疫応答の分子制御機構の解明が強く求められている。本研究は、好中球の分化および機能獲得を制御する遺伝子産物PPM1Dを同定し、その詳細な機能を明らかとした。本研究により、好中球分化および機能制御機構の破綻により引き起こされる様々な疾患の原因解明・新規治療法開発への展開が期待される。
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Report
(3 results)
Research Products
(24 results)
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[Journal Article] On the role of H3.3 in retroviral silencing2017
Author(s)
Wolf Gernot、Rebollo Rita、Karimi Mohammad M.、Ewing Adam D.、Kamada Rui、Wu Warren、Wu Brenda、Bachu Mahesh、Ozato Keiko、Faulkner Geoffrey J.、Mager Dixie L.、Lorincz Matthew C.、Macfarlan Todd S.
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Journal Title
Nature
Volume: 548
Issue: 7665
Pages: E1-E3
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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