Fiche publication
Date publication
mars 2021
Journal
EMBO reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr NEGRONI Luc
Tous les auteurs :
Sicari D, Centonze FG, Pineau R, Le Reste PJ, Negroni L, Chat S, Mohtar MA, Thomas D, Gillet R, Hupp T, Chevet E, Igbaria A
Lien Pubmed
Résumé
In the past decades, many studies reported the presence of endoplasmic reticulum (ER)-resident proteins in the cytosol. However, the mechanisms by which these proteins relocate and whether they exert cytosolic functions remain unknown. We find that a subset of ER luminal proteins accumulates in the cytosol of glioblastoma cells isolated from mouse and human tumors. In cultured cells, ER protein reflux to the cytosol occurs upon ER proteostasis perturbation. Using the ER luminal protein anterior gradient 2 (AGR2) as a proof of concept, we tested whether the refluxed proteins gain new functions in the cytosol. We find that refluxed, cytosolic AGR2 binds and inhibits the tumor suppressor p53. These data suggest that ER reflux constitutes an ER surveillance mechanism to relieve the ER from its contents upon stress, providing a selective advantage to tumor cells through gain-of-cytosolic functions-a phenomenon we name ER to Cytosol Signaling (ERCYS).
Mots clés
ER stress, ERAD, cancer, endoplasmic reticulum, reflux
Référence
EMBO Rep. 2021 Mar 12;:e51412
