Interaktom translačního iniciačního faktoru eIF4E2

Lettrich, Patrik

Regulation of gene expression at the level of translation is one of the most prominent processes when it comes to maintaining cellular vital functions in physiolgical norm. Initiation phase plays an especially important role in translational regulation. Majority of eukaryotic mRNAs possess methylguanosine cap on its 5' end. Binding of initiation factor eIF4E1 to cap is substantial part of canonical mechanism of translational initiation. eIF4E1 is component of bigger complex termed eIF4F, whose association with cap mRNA is essential for initiation of translation. Due to cap-binding ability of noncanonical initiation factors and their interaction partners, that are distinct from those of eIF4E1, there can occur specific regulation of translational initiation. One of these noncanonical factors is eIF4E2. In regulatory processes it mostly acts as a translational repressor. Binding of eIF4E2 to cap impedes association of eIF4F complex with mRNA, and therefore inhibits translation. However, eIF4E2 is also able to promote cap-dependent initiation of translation using an alternative mechanism in hypoxic conditions. This thesis represents the first complex analysis of protein-protein interactions and physiological functions of factor eIF4E2 and its homologs in several model organisms. Key words:...

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