SILAC-based quantitative proteomics of endoplasmic reticulum stress

ABSTRACT: ER stress and the unfolded protein response (UPR) involve extensive proteome remodeling in many cell compartments. However, a comprehensive analysis has been lagging due to technological limitations. Here we employ SILAC-based proteomics to quantify over 6,200 proteins at increasing concentrations of tunicamycin in HeLa cells. We further compare the effects of tunicamycin to those of thapsigargin and DTT, both activating the UPR through different mechanisms. The systematic description of the proteome-wide expression changes following proteostatic stress is a resource for the scientific community, which enables to discover novel players involved the pathophysiology of disorders linked to proteostasis. Here, we identified 38 proteins, not previously linked to the UPR, whose expression increases, of which 15 would likely remediate ER stress, and the remainder may contribute to pathological outcomes. Unexpectedly, we see few strongly downregulated proteins, despite expression of the pro-apoptotic transcription factor CHOP, suggesting that IRE1-dependent mRNA decay (RIDD) has a limited contribution to ER-stress mediated cell death in our system.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Uterine Cervix

SUBMITTER: Marta Murgia  

LAB HEAD: Marta Murgia

PROVIDER: PXD013496 | Pride | 2019-11-01

REPOSITORIES: Pride