Human cells contain three eIF4E protein isoforms encoded by separate genes. Each is capable of binding to the 5’ mRNA cap and exists in several variants resulting from alternative mRNA splicing. All eIF4E isoforms play important roles in development, cancer, cellular response to stress and virus infection. Cellular level and activity of the canonical eIF4E1 are tightly regulated by mTOR and Mnk kinases. Overexpression of eIF4E1 can lead to cellular transformation and indeed up to one third of human cancers show an increase in eIF4E1 levels. In addition to its well-recognized role in mRNA silencing and translation in hypoxia, the non-canonical eIF4E2 is one of the proteins whose deregulation creates part of the signature of metastatic cells. In contrast, eIF4E3 has been proposed to act as a tumor suppressor protein. The aim of the proposed project is to use advanced pull-down and chromatography methods followed by LC-MS to purify, analyze and characterize active protein complexes in which the non-canonical members of the eIF4E family occur in human cells upon infection of viruses.
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