Studying the Role of Eukaryotic Translation Initiation Factor 4E (eIF4E) Phosphorylation by MNK1/2 Kinases in Prostate Cancer Development and Progression

The mRNA cap-binding protein eukaryotic initiation factor 4E eIF4E plays a key role in cancer progression. We have recently shown Furic et al., 2010 that phosphorylation of eIF4E at Ser209 by the MNK family of kinases promotes prostate cancer progression in a mouse model bearing a tissue-specific conditional PTEN deletion in prostatic epithelia. eIF4E activity is regulated at two levels phosphorylation of Ser209 and binding to a family of small eIF4E-binding proteins aptly termed 4EBPs. Binding of 4E-BPs to eIF4E precludes eIF4G binding thus preventing assembly of the eIF4F complex and recruitment of the ribosome to the messenger RNA. Our most recent data suggests that PTEN interacts genetically with 4E-BPs to induce cellular senescence in prostate cancer. In this report, we also begin to address the effects of simultaneous inhibition of MNK and mTORC1 activity in anchorage-independent prostate cancer cell lines. Our findings will hopefully yield important information for the design of effective therapeutic agents against human prostate cancer.