Targeting Mnk/eIF4E pathway for cancer therapy

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MAP kinase-interacting kinase 1 (Mnk1) and Mnk2 are protein-serine/threonine kinases that are activated by ERK or p38 and phosphorylate a translation initiation factor eIF4E. We have previously reported that Mnk1/2 double deficiency delays tumor development in a mouse lymphoma model and that suppression of Mnk1 significantly reduces the tumorigenic activity of xenografted human glioma cells. To further investigate the regulatory network of Mnks, we attempted to search for Mnk1- interacting proteins. The Flag-tagged wild-type Mnk1 and kinase-dead Mnk1 complexes were affinity-purified from mouse embryonic fibroblasts, and then the identities of binding proteins were determined by tandem mass spectrometry. As a result, a 130kDa deubiquitinase was identified as a novel Mnk1-binding partner. We are currently exploring the impact of the interaction between these proteins.