eIF4E--from translation to transformation.
Over the years, studies have focused on the transcriptional regulation of oncogenesis. More recently, a growing emphasis has been placed on translational control. The Ras and Akt signal transduction pathways play a critical role in regulating mRNA translation and cellular transformation. The question arises: How might the Ras and Akt signaling pathways affect translation and mediate transformation? These pathways converge on a crucial effector of translation, the initiation factor eIF4E, which binds the 5'cap of mRNAs. This review focuses on the role of eIF4E in oncogenesis. eIF4E controls the translation of various malignancy-associated mRNAs which are involved in polyamine synthesis, cell cycle progression, activation of proto-oncogenes, angiogenesis, autocrine growth stimulation, cell survival, invasion and communication with the extracellular environment. eIF4E-mediated translational modulation of these mRNAs plays a pivotal role in both tumor formation and metastasis. Interestingly, eIF4E activity is implicated in mitosis, embryogenesis and in apoptosis. Finally, the finding that eIF4E is overexpressed in several human cancers makes it a prime target for anticancer therapies.
Mamane
Yaël
Y
Department of Biochemistry, McGill Cancer Centre, McGill University, 3655 Promenade Sir-William-Osler, Montreal, Quebec, Canada, H3G 1Y6.
Petroulakis
Emmanuel
E
Rong
Liwei
L
Yoshida
Kaori
K
Ler
Lian Wee
LW
Sonenberg
Nahum
N
D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D019938:Cyclin D1 / Q000235:genetics; D039561:Eukaryotic Initiation Factor-4E / Q000502:physiology*; D016259:Genes, myc; D006801:Humans; D020935:MAP Kinase Signaling System; D014176:Protein Biosynthesis; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D039561:Eukaryotic Initiation Factor-4E; D042461:Vascular Endothelial Growth Factor A; D019938:Cyclin D1