title: Tuning Specific Translation in Cancer Metastasis and Synaptic Memory: Control at the MNK-eIF4E Axis.
abstract: The eukaryotic translation initiation factor (eIF) 4E, which binds to the 5'-cap of mRNA, undergoes phosphorylation on a single conserved serine, executed by the mitogen-activated protein kinase (MAPK)-interacting kinases (MNKs). However, the functional consequences and physiological roles of MNK signalling have remained obscure. Now, new pharmacological and genetic tools have provided unprecedented insights into the function of MNKs and eIF4E phosphorylation. The studies suggest that MNKs control the translation of specific mRNAs in cancer metastasis and neuronal synaptic plasticity by a novel mechanism involving the regulation of the translational repressor, cytoplasmic fragile-X protein-interacting protein 1 (CYFIP1). These recent breakthroughs go a long way to resolving the longstanding enigma and controversy surrounding the function of the MNK-eIF4E axis in cancer cell biology and neurobiology.
authors.affiliation: Department of Biomedicine and KG Jebsen Centre for Neuropsychiatric Disorders, University of Bergen, 5009 Bergen, Norway. Electronic address: Clive.bramham@biomed.uib.no.
authors.forename: Clive R
authors.initials: CR
authors.lastname: Bramham
authors.affiliation: South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia; School of Biological Sciences, University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: Kirk B
authors.initials: KB
authors.lastname: Jensen
authors.affiliation: South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia; School of Biological Sciences, University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Proud
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009473:Neuronal Plasticity; D010766:Phosphorylation; D011485:Protein Binding; D014176:Protein Biosynthesis; D012315:RNA Caps / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013569:Synapses / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C109916:CYFIP1 protein, human; D039561:Eukaryotic Initiation Factor-4E; D012315:RNA Caps
keywords: Autism spectrum disorders.; MAP kinase-interacting kinase; cytoplasmic fragile-X mental retardation protein; epithelial-mesenchymal transition; long-term synaptic plasticity; protein synthesis