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Analyses structurales et fonctionnelles des interactions entre elF4E et ses partenaires

Abstract : The control of mRNA translation is a complex process that is critical for gene expression during development and many physiological processes. During translation initiation in eukaryotes, the Initiation Factor 4E (eIF4E) binds the cap structure of the mRNA and recruits the large scaffolding protein eIF4G to form the initiation complex, step that is often the major site of protein synthesis control. Interaction between eIF4E and eIF4G is targeted by the small translational repressor 4E-BP and other specific eIF4E-interacting partners (4E-IPs), which share with eIF4G a similar eIF4E-binding motif and compete for eIF4E to modulate its functions at different levels. Commonly, the repressor 4E-BP is described as a completely disordered protein, even in its eIF4E-bound state. In the present work, we showed that 4E-BP adopts in fact a folded structure when it interacts with eIF4E, establishing fuzzy and dynamic contacts that involve a larger binding footprint of 4E-BP on eIF4E.These results brought new insight into the mechanisms involved in the interaction between eIF4E and its partners, and emphasized the role of structural studies to develop new therapies, particularly in cancer treatments. During my thesis, we also developed a new approach that combines structural, in silico and biochemical analyses to find novel 4E-IPs. Among the new putative 4E-IPs, we characterized Angel1, a protein related to a family of deadenylases. All together, these results have opened up new perspectives in term of mRNA metabolism and specific regulations that target eIF4E
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Submitted on : Monday, June 3, 2013 - 12:32:49 PM
Last modification on : Thursday, December 10, 2020 - 10:53:51 AM
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  • HAL Id : tel-00829452, version 1


Pauline Gosselin. Analyses structurales et fonctionnelles des interactions entre elF4E et ses partenaires. Biologie cellulaire. Université Pierre et Marie Curie - Paris VI, 2012. Français. ⟨NNT : 2012PAO66201⟩. ⟨tel-00829452⟩



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