title: The eukaryotic translation initiation factor eIF4E in the nucleus: taking the road less traveled.
abstract: The eukaryotic translation initiation factor eIF4E is a potent oncogene. Although eIF4E has traditional roles in translation initiation in the cytoplasm, it is also found in the nucleus, suggesting that it has activities beyond its role in protein synthesis. The road less traveled has been taken to study these nuclear activities and to understand their contribution to the oncogenic potential of eIF4E. The molecular features and biological pathways underpinning eIF4E's nuclear mRNA export are described. New classes of eIF4E regulators have been identified and their relevance to cancer shown. The studies presented here reveal the molecular, biophysical, and structural bases for eIF4E regulation. Finally, recent clinical work targeting eIF4E in acute myeloid leukemia patients with ribavirin is discussed. In summary, these findings provide a novel paradigm for eIF4E function and the molecular basis for targeting it in leukemia patients.
authors.affiliation: Institute for Research in Immunology and Cancer & Dept. of Pathology and Cell Biology, Université de Montréal, Montréal, QC, Canada.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Osborne
authors.forename: Katherine L B
authors.initials: KL
authors.lastname: Borden
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D002467:Cell Nucleus / Q000378:metabolism*; D002986:Clinical Trials as Topic; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000276:immunology*; D058990:Molecular Targeted Therapy; D021381:Protein Transport; D012254:Ribavirin / Q000627:therapeutic use; D015398:Signal Transduction
chemical_list: D039561:Eukaryotic Initiation Factor-4E; D012254:Ribavirin
keywords: PML; clinical trials; eIF4E; mRNA export; ribavirin