Inadequate BiP availability defines endoplasmic reticulum stress.

ABSTRACT: How endoplasmic reticulum (ER) stress leads to cytotoxicity is ill-defined. Previously we showed that HeLa cells readjust homeostasis upon proteostatically driven ER stress, triggered by inducible bulk expression of secretory immunoglobulin M heavy chain (μ_s) thanks to the unfolded protein response (UPR; Bakunts et al., 2017). Here we show that conditions that prevent that an excess of the ER resident chaperone (and UPR target gene) BiP over µ_s is restored lead to µ_s-driven proteotoxicity, i.e. abrogation of HRD1-mediated ER-associated degradation (ERAD), or of the UPR, in particular the ATF6α branch. Such conditions are tolerated instead upon removal of the BiP-sequestering first constant domain (C_H1) from µ_s. Thus, our data define pr

SUBMITTER: Vitale M 

PROVIDER: S-EPMC6417858 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature