Mnks, eIF4E phosphorylation and cancer

Abstract

The MAP kinase signal-integrating kinases or MAP kinase-interacting protein kinases (Mnks) are activated by signaling through the oncogenic MAP kinase (ERK) pathway. The best-known Mnk substrate is eukaryotic initiation factor eIF4E, the protein which binds the 5'-cap structure of eukaryotic mRNAs and helps to recruit ribosomes to them. eIF4E is a well-established proto-oncogene, whose expression or activation is associated with transformation and tumorigenesis. Mnks phosphorylate eIF4E at a single site. Increasing evidence implicates the Mnks and/or phosphorylation of eIF4E in cell transformation, tumorigenesis or tumor progression, in a growing range of settings. Mnks and/or the phosphorylation of eIF4E have been suggested to regulate the expression of proteins involved in cell cycle progression, cell survival and cell motility. Further work is needed to extend our understanding of the impact of the Mnks on gene expression, explore the biochemical mechanisms involved and evaluate the utility of targeting the Mnks in cancer therapy. This article is part of a Special Issue entitled: Translation and Cancer.

Keywords: ERK; Initiation factor; Tumorigenesis; mRNA translation; mTOR.