Journal article
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 (μs) 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 µs is restored lead to µs-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 (CH1) from µs. Thus, our data define proteostatic ER stress to be a specific consequence of inadequate BiP availability, which both the UPR and ERAD redeem.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 18.0MB, Terms of use)
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- Publisher copy:
- 10.7554/eLife.41168.001
Authors
- Publisher:
- eLife Sciences Publications
- Journal:
- eLife More from this journal
- Volume:
- 8
- Pages:
- e41168
- Publication date:
- 2019-03-14
- Acceptance date:
- 2019-02-13
- DOI:
- EISSN:
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2050-084X
- Keywords:
- Pubs id:
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pubs:971914
- UUID:
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uuid:c671d579-f78d-43c6-bb43-50fc287a38de
- Local pid:
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pubs:971914
- Source identifiers:
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971914
- Deposit date:
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2019-02-13
- ARK identifier:
Terms of use
- Copyright holder:
- Vitale et al
- Copyright date:
- 2019
- Notes:
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© 2019, Vitale et al.
This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
- Licence:
- CC Attribution (CC BY)
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