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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    • "The activation of UBF is regulated by the cell cycle regulator cyclin D1, which in turn is translationally regulated by MNK1-eIF4E signaling (Mamane et al. 2004;Topisirovic et al. 2004). In the current study, RE strongly activated the MNK1-eIF4E-cyclin D1 axis. "
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