eIF4E appears to mediate the export of a pair of mRNAs from the nucleus to the cytoplasm, these generally include mRNAs for several proteins associated with cell cycle progression or cell survival. Phosphorylation of eIF4E by Mnks may also be very important to its role in the export of some mRNAs, e. g., purchase Oprozomib cyclin D and hdm2, providing an additional mechanism where phosphorylation of eIF4E may promote tumourigenesis. Drosophila expressing a mutant eIF4E in which Ser251, the residue which corresponds to the Ser209 of mammalian eIF4E is mutated to alanine, show paid off viability. By contrast, mice with deletions in both Mnk1 and Mnk2 develop normally without detectable eIF4E phosphorylation. Recent studies confirmed skeletal systems whilst it is dispensable in normal tissue, that phosphorylation of eIF4E at the Ser209 by Mnk is vital for eIF4Es ability to increase tumourigenesis. In a classy study, a mouse model where lymphomas generated from Eu Myc transgenic HSCs were transfected with wild-type eIF4E and eIF4E mutants, was used to analyze their effects on oncogenicity. Wild type eIF4E greatly enhanced Myc mediated lymphomagenesis compared to animals expressing eIF4E Trp56Ala, a mutant with defective cap binding ability, implying an important oncogenic purpose for eIF4E. Similarly, mice reconstituted with cells carrying the mutant were faulty in tumor growth to a similar extent to the mice, indicating that phosphorylation of Ser209 is vital for eIF4E mediated tumourigenesis. Conversely, activated Mnk1 promoted the Cathepsin Inhibitor 1 on-set of tumour growth in a similar fashion to eIF4E. Mnk1 and eIF4E revealing lymphomas showed low levels of apoptosis when compared with control tumours. This was related to the capacity of eIF4E or Mnk1 to improve the expression of the anti apoptotic protein Mcl 1, and it was shown that Mnk1 mediated phosphorylation of eIF4E at Ser209 correlated with the level of Mcl 1 expression. Further study of the link between Mnk1/2 and tumourigenesis driven by lack of PTEN demonstrated that Mnk1/2 double knock out tPTEN mice showed attenuated tumor development in comparison with the parental tPTEN mice. Phosphorylation of eIF4E was greatly enhanced in lymphomas from tPTEN mice compared with lymphoid tissues of wild-type mice, but was removed in lymphomas of tPten, Mnk1/2 double knock out mice, confirming that Mnk1 and Mnk2 kinase activity are crucial for eIF4E phosphorylation in transformed cells. This is consistent with the high degrees of Mnk1 and eIF4E phosphorylation shown by human glioma U87MG cells displaying an inactivating PTEN mutation. Conversely, U87MG cells where Mnk1 have been knocked down by shRNA showed significantly paid down quantities of phosphorylated eIF4E and substantially decreased tumour formation.