Phosphorylation of the eukaryotic translation initiation factor eIF4E contributes to its transformation and mRNA transport activities

NYU Langone Medical Center, New York, New York, United States
Cancer Research (Impact Factor: 9.33). 01/2005; 64(23):8639-42. DOI: 10.1158/0008-5472.CAN-04-2677
Source: PubMed


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.

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Available from: Katherine Borden, Jan 12, 2015
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    • "Sumoylation did not interfere with mRNA recognition but enhanced eIF4F complex assembly on the mRNA cap, promoting the expression of ornithine decarboxylase, c-myc and Bcl-2, driving the anti-apoptotic and oncogenic activity of eIF4E [33]. As phosphorylation of eIF4E has been shown to play a role in selective nuclear export of mRNA [71], it is likely that sumoylation of eIF4E occurs in the nucleus and/or as it emerges into the cytoplasm "
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    • "Further, eIF4E enhances the mRNA export of a subset of transcripts also involved in proliferation and survival which increases their cytoplasmic levels and thus their availability to the translation machinery. Both of these activities are stimulated by the phosphorylation of eIF4E which occurs via Mnk kinase [55,56,57,58,59]. Thus, targeting PI3K, Akt, Mnk and eIF4E are all reasonable strategies to target these processes.Cancer cells appear to develop an oncogene addiction to eIF4E thereby providing a therapeutic window for targeting this protein [32,60,61]. "
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