Thèse soutenue

Les proteines Mex-3 humaines : de nouveaux acteurs dans les voies de régulation des ARN
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Auteur / Autrice : Julien Courchet
Direction : Marc Billaud
Type : Thèse de doctorat
Discipline(s) : Biologie
Date : Soutenance en 2008
Etablissement(s) : Lyon 1

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Résumé

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LKB1 is a tumour suppressor protein kinase controlling energetic metabolism and cell polarity. In order to gain insight into the mechanism by which LKB1 is involved in these functions, we have identified a novel family of four related but distinct human genes (hMex-3A to 3D) orthologous to Caenorhabditis elegans mex-3 gene. HMex-3 genes encode RNA-binding phospho-proteins, two of them (hMex-3A and hMex-3B) being differentially localized in cytoplasmic foci involved in mRNA sorting and decay. Global proteomic approach by affinity purification of protein complexes led to the identification of hMex-3B and 3C interacting proteins amongst which most are known to be involved in mRNA metabolism. We subsequently focused on the binding of the 14-3-3 adaptor proteins, which is specific to hMex-3B, and demonstrated that this interaction regulates hMex-3B stability, mRNA binding and sorting to distinct classes of RNA granules. To conclude, this manuscript presents results concerning the newly described Mex-3 proteins family, which are new regulators of mRNA metabolism. Preliminary results suggest that these proteins are downstream effectors of LKB1, an hypothesis that will be followed-up by further investigations of the functional links between hMex-3 proteins, LKB1 and cell polarity