title: Phosphorylation of the eukaryotic translation initiation factor eIF4E contributes to its transformation and mRNA transport activities.
abstract: The eukaryotic translation initiation factor eIF4E is dysregulated in a wide variety of human cancers. In the cytoplasm, eIF4E acts in the rate-limiting step of translation initiation whereas in the nucleus, eIF4E forms nuclear bodies and promotes the nucleo-cytoplasmic export of a subset of growth-promoting mRNAs including cyclin D1. The only known post-translational modification of eIF4E is its phosphorylation at S209. Many studies have examined the role of phosphorylation on cap-dependent translation. However, no studies to date have explored the role of phosphorylation on the ability of eIF4E to transform cells. Using mutagenesis and separately a small molecular inhibitor of eIF4E phosphorylation, we show that eIF4E phosphorylation enhances both its mRNA transport function and its transformation activity in cell culture. Thus, phosphorylation of nuclear eIF4E seems to be an important step in control of the mRNA transport and thus the transforming properties of eIF4E.
authors.affiliation: Structural Biology Program, Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York University, New York, New York, USA.
authors.forename: Ivan
authors.initials: I
authors.lastname: Topisirovic
authors.forename: Melisa
authors.initials: M
authors.lastname: Ruiz-Gutierrez
authors.forename: Katherine L B
authors.initials: KL
authors.lastname: Borden
mesh_terms: D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics; D039561:Eukaryotic Initiation Factor-4E / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016296:Mutagenesis; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D011687:Purines / Q000494:pharmacology; D034443:RNA Transport / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D000814:Aniline Compounds; C466997:CGP 57380; D039561:Eukaryotic Initiation Factor-4E; D011687:Purines; D012333:RNA, Messenger; D019938:Cyclin D1