Abstract
The biosynthesis of about one third of the human proteome, including membrane receptors and secreted proteins, occurs in the endoplasmic reticulum (ER). Conditions that perturb ER homeostasis activate the unfolded protein response (UPR). An ‘optimistic’ UPR output aims at restoring homeostasis by reinforcement of machineries that guarantee efficiency and fidelity of protein biogenesis in the ER. Yet, once the UPR ‘deems’ that ER homeostatic readjustment fails, it transitions to a ‘pessimistic’ output, which, depending on the cell type, will result in apoptosis. In this article, we discuss emerging concepts on how the UPR ‘evaluates’ ER stress, how the UPR is repurposed, in particular in B cells, and how UPR-driven counter-selection of cells undergoing homeostatic failure serves organismal homeostasis and humoral immunity.
Original language | English (US) |
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Pages (from-to) | 529-541 |
Number of pages | 13 |
Journal | Trends in Cell Biology |
Volume | 31 |
Issue number | 7 |
DOIs | |
State | Published - Jul 2021 |
Keywords
- B cell development
- RIDD
- antibody production
- endoplasmic reticulum
- proteostasis
- unfolded protein response
- Immunity, Humoral
- Endoplasmic Reticulum Stress
- Humans
- Homeostasis
- Unfolded Protein Response
- Endoplasmic Reticulum/metabolism
ASJC Scopus subject areas
- Cell Biology