Fiche publication
Date publication
septembre 2020
Journal
Cancers
Auteurs
Membres identifiés du Cancéropôle Est :
Dr JEGO Gaëtan
Tous les auteurs :
Miloudi H, Bohers É, Guillonneau F, Taly A, Gibouin VC, Viailly PJ, Jego G, Grumolato L, Jardin F, Sola B
Lien Pubmed
Résumé
The gene encodes exportin 1 (XPO1) that controls the nuclear export of cargo proteins and RNAs. Almost 25% of primary mediastinal B-cell lymphoma (PMBL) and classical Hodgkin lymphoma (cHL) cases harboured a recurrent point mutation (NM_003400, chr2:g61718472C>T) resulting in the E571K substitution within the hydrophobic groove of the protein, the site of cargo binding. We investigated the impact of the mutation using PMBL/cHL cells having various statuses and CRISPR-Cas9-edited cells in which the E571K mutation was either introduced or knocked-out. We first confirmed that the mutation was present in both XPO1 mRNA and protein. We observed that the mutation did not modify the export capacity but rather the subcellular localisation of XPO1 itself. In particular, mutant XPO1 bound to importin β1 modified the nuclear export/import dynamics of relevant cargoes.
Mots clés
B-cell lymphoma, CRISPR–Cas9, XPO1/CRM1, importin β1, indirect immunofluorescence, nuclear export, nuclear import, proteomics, proximity ligation assay
