title: The oncogene eIF4E: using biochemical insights to target cancer.
abstract: The eukaryotic translation initiation factor eIF4E is overexpressed in many human malignancies where it is typically a harbinger of poor prognosis. eIF4E is positioned as a nexus in post-transcriptional gene expression. To carry out these functions, eIF4E needs to bind the m(7)G cap moiety on mRNAs. It plays critical roles in mRNA translation, mRNA export, and most likely in mRNA stability as well. Through these activities, eIF4E coordinately modulates the expression of many transcripts involved in proliferation and survival. eIF4E function is controlled by interactions with protein cofactors in concert with many signaling pathways, including Ras, Mnk, Erk, MAPK, PI3K, mTOR, and Akt. This review describes the eIF4E activity and provides several examples of cellular control mechanisms. Further, we describe some therapeutic strategies in preclinical and clinical development.
authors.affiliation: Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA 19104, USA. carroll2@mail.med.upenn.edu
authors.forename: Martin
authors.initials: M
authors.lastname: Carroll
authors.forename: Katherine L B
authors.initials: KL
authors.lastname: Borden
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D009857:Oncogenes; D015398:Signal Transduction / Q000235:genetics
chemical_list: D039561:Eukaryotic Initiation Factor-4E