The eukaryotic translation
initiation factor eIF4E is a potent oncogene. In fact, its overexpression in human
cancer often correlates with poor prognosis. Traditionally,
eIF4E plays a role in translation initiation where it binds the 5' m7G cap found on mRNAs. More recent studies indicate that a significant fraction of
eIF4E (up to 68%) resides in the nucleus where it regulates the nuclear export of specific mRNAs. Additionally,
eIF4E may play a role in
mRNA sequestration and stability in cytoplasmic processing bodies (P-bodies). Our recent studies suggest that
eIF4E governs cell cycle progression and cellular proliferation by coordinately orchestrating the expression of several genes at the post-transcriptional level. Hence,
eIF4E functions as a central node of an
RNA regulon (described below), which plays an essential role in normal differentiation and development and is frequently dysregulated in
cancer. Several cellular factors, such as the
promyelocytic leukemia protein PML, modulate the function of this regulon by altering the activity of
eIF4E. Here, the physiological implications of these observations are described and the clinical implications of directly targeting
eIF4E, and the related regulon, are discussed.