Post-translational modification by symmetric ariginine dimetylation in immune regulation and diseases
| Project/Area Number |
25293066
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Showa University (2015-2016)
The University of Tokyo (2014)
Tokyo Medical and Dental University (2013) |
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Principal Investigator |
Koga Takako 昭和大学, 歯学部, 講師 (90451905)
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| Project Period (FY) |
2013-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2015: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2014: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Fiscal Year 2013: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
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| Keywords | 破骨細胞 / 免疫系細胞 / タンパク質翻訳後修飾 / 生体恒常性 / アルギニンメチル化 / タンパク質修飾 / 細胞分化 / 生体制御 / メチル化 / タンパク質メチル化酵素 / シグナル伝達 / 翻訳語修飾 / 転写因子 / 生体分子医学 / 生体分子 / 免疫 / 発生 |
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| Outline of Final Research Achievements |
Protein arginine methylation is a post-translational modification which contributes to a wide range of biological processes such as transcriptional control and mRNA splicing. Mice lacking PRMT5 specifically in osteoclasts showed an decreased bone mass due to an increased bone resorption. In addition, T cell-specific deletion of the Prmt5 gene led to a marked reduction in gamma chain family cytokine signaling and a severe loss of thymic iNKT cells and a decreased number of peripheral CD4+ and CD8+ T cells. PRMT5 induces the symmetric dimethylation of Sm proteins which promote the splicing of the Il2rg pre-mRNA, critically contributing to the expression of gamma chain. These findings demonstrate that arginine methylation plays a key role in the regulation of gamma chain family cytokine signaling strength by facilitating the expression of signal-transducing components.
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Report
(4 results)
Research Products
(5 results)
