Reflux of Endoplasmic Reticulum proteins to the cytosol yields inactivation of tumor suppressors

ABSTRACT: 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 found that select ER luminal proteins accumulate 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. As such we investigated whether refluxed proteins gain new functions in the cytosol, a mechanism that could provide advantage to tumor cells. Using the ER luminal protein AGR2 as a proof of concept, we showed that it is refluxed to the cytosol where it binds and inhibits the tumor suppressor p53. We named this phenomenon ER to Cytosol Signaling (ERCYS) as an ER surveillance mechanism conserved in Eukaryotes to relieve the ER from its contents upon stress that has evolved to provide selective advantage to tumor cells through gain-of-cytosolic functions.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Suspension Culture, Permanent Cell Line Cell, Glioblastoma Multiforme Cell

DISEASE(S): Brain Cancer

SUBMITTER: Luc Negroni  

LAB HEAD: Eric Chevet

PROVIDER: PXD023567 | Pride | 2021-05-03

REPOSITORIES: Pride