Molecular mechanism of translational regulation mediated by the crosstalk between mTOR and Mnk signaling pathways in tumorigenesis

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K07953
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Osaka University of Pharmaceutical Sciences
• Principal Investigator: Fukunaga Rikiro 大阪薬科大学, 薬学部, 教授(移行) (40189965)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: シグナル伝達 / プロテインキナーゼ / 細胞増殖 / 翻訳制御 / MAPキナーゼ

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.

Free Research Field

分子細胞生物学