Controlling gene expression through RNA regulons: the role of the eukaryotic translation initiation factor eIF4E.
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.
Culjkovic
Biljana
B
Institute for Research in Immunology and Cancer, Department of Pathology and Cell Biology, Université de Montréal, Montréal, Québec, Canada.
Topisirovic
Ivan
I
Borden
Katherine L B
KL
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D039561:Eukaryotic Initiation Factor-4E / Q000502:physiology*; D039642:Eukaryotic Initiation Factors / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D009369:Neoplasms; D012313:RNA / Q000096:biosynthesis* / Q000235:genetics; D018085:Regulon / Q000502:physiology*
D039561:Eukaryotic Initiation Factor-4E; D039642:Eukaryotic Initiation Factors; D012313:RNA