Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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Outline of Final Research Achievements |
To investigate translational regulation in tumor cell growth, we generated HeLa cells lacking the Mnk1 and/or Mnk2 genes by using the CRISPR/Cas9 method. We found that inhibition of mTORC1 resulted in upregulation of eIF4E phosphorylation and that this signal crosstalk was mediated by Mnk2 but not by Mnk1. We also found that stimulation of cells by growth factors resulted in upregulation of Mnk1-mediated phosphorylation of eIF4E but in suppression of Mnk2-mediated eIF4E phosphorylation, suggesting that Mnk2 is regulated, at least in part, by an unidentified mechanism that would be different from the MAPK pathway but linked to the PI3K-mTOR pathway. This study would raise the potential for combination treatments of mTOR and Mnk inhibitors for tumor therapies.
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