Inadequate BiP availability defines endoplasmic reticulum stress

Autor: Anush Bakunts, Andrea Orsi, Alberto Danieli, Laura Tadè, Roberto Sitia, Andrea Raimondi, Milena Vitale, Eelco van Anken, Federica Lari, Claudia Rato, John C. Christianson, Caterina Valetti
Přispěvatelé: Vitale, Milena, Bakunts, Anush, Orsi, Andrea, Lari, Federica, Tadè, Laura, Danieli, Alberto, Rato, Claudia, Valetti, Caterina, Sitia, Roberto, Raimondi, Andrea, Christianson, John C., van Anken, Eelco, VAN ANKEN, Eelco, Vitale, Milena [0000-0001-7007-402X], Bakunts, Anush [0000-0001-8793-1999], Orsi, Andrea [0000-0003-2839-1640], Lari, Federica [0000-0003-2789-7877], Rato, Claudia [0000-0002-3971-046X], Valetti, Caterina [0000-0003-2917-1586], Sitia, Roberto [0000-0001-7086-4152], Raimondi, Andrea [0000-0002-4563-386X], Christianson, John C [0000-0002-0474-1207], van Anken, Eelco [0000-0001-9529-2701], Apollo - University of Cambridge Repository
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Immunology and Microbiology (all)
0302 clinical medicine
cell biology
chaperone
Biology (General)
Cytotoxicity
Endoplasmic Reticulum Chaperone BiP
Heat-Shock Proteins
biology
Chemistry
General Neuroscience
proteotoxicity
Endoplasmic Reticulum-Associated Degradation
General Medicine
unfolded protein response
Endoplasmic Reticulum Stress
BiP/GRP78
ER stress
chaperones
endoplasmic reticulum
human
Cell biology
ER stre
Medicine
Human
QH301-705.5
Constant domain
Science
macromolecular substances
Endoplasmic-reticulum-associated protein degradation
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
Humans
Neuroscience (all)
Biochemistry
Genetics and Molecular Biology (all)
General Immunology and Microbiology
Endoplasmic reticulum
Epithelial Cells
Cell Biology
030104 developmental biology
Proteotoxicity
Chaperone (protein)
Proteostasis
biology.protein
Unfolded protein response
Research Advance
030217 neurology & neurosurgery
Homeostasis
HeLa Cells
Zdroj: eLife, Vol 8 (2019)
eLife
Popis: 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.
Databáze: OpenAIRE
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