| Project/Area Number |
15K19140
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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 |
Immunology
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| Research Institution | Okinawa Institute of Science and Technology Graduate University |
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Principal Investigator |
Kureha Taku 沖縄科学技術大学院大学, 細胞シグナルユニット, 研究員 (50637684)
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | T細胞分化 / 正の選択 / 脱アデニル化 / CCR4-NOT複合体 / TCRシグナル / CCR4-NOT / deadenylation / positive selection |
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| Outline of Final Research Achievements |
Positive selection of double-positive (DP) thymocytes requires precise regulations of T-cell antigen receptor (TCR) signaling. We here describe that limitation of mRNA poly (A) tail length by the deadenylase CCR4-NOT complex ensures the positive selection by modulating TCR signaling. The CCR4-NOT complex is the major deadenylase that removes poly(A) tails from mRNAs. To clarify the role of CNOT3 in T cell, we generated mice devoid of CNOT3 in T cell specific manner. T cell-specific depletion of the CNOT3 subunit revealed requirements of the CCR4-NOT complex in the positive selection and inhibition of inappropriate Jnk and p38 activations induced by TCR stimulation. Furthermore, we found that the CCR4-NOT complex post-transcriptionally attenuates expression of ASK1, thereby preventing inappropriate activation of Jnk and p38 after TCR stimulation. Consequently, our data suggest a novel link between the deadenylase-mediated poly(A) tail shortening and the T cell repertoire formation.
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