Inadequate BiP availability defines endoplasmic reticulum stress.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30869076.
- Also identified by DOI 10.7554/eLife.41168 and PMC identifier 6417858.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sub>s</sub>) 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<sub>s</sub> is restored lead to µ<sub>s</sub>-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<sub>H</sub>1) from µ<sub>s</sub>. Thus, our data define proteostatic ER stress to be a specific consequence of inadequate BiP availability, which both the UPR and ERAD redeem.
Medical subject headings
- Endoplasmic Reticulum Stress
- Epithelial Cells
- Heat-Shock Proteins