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Cited by 800

The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.

Adaptation to ER Stress Is Mediated by Differential Stabilities of Pro-Survival and Pro-Apoptotic mRNAs and Proteins

Open access
Rutkowski, D. Thomas, Arnold, Stacey M, Miller, Corey N, Wu, Jun, Li, Jack, Gunnison, Kathryn M, Mori, Kazutoshi, Sadighi Akha, Amir A., Raden, David, Kaufman, Randal J·2006·PLoS Biology

Abstract

The accumulation of unfolded proteins in the endoplasmic reticulum (ER) activates a signaling cascade known as the unfolded protein response (UPR). Although activation of the UPR is well described, there is little sense of how the response, which initiates both apoptotic and adaptive pathways, can selectively allow for adaptation. Here we describe the reconstitution of an adaptive ER stress response in a cell culture system. Monitoring the activation and maintenance of representative UPR gene expression pathways that facilitate either adaptation or apoptosis, we demonstrate that mild ER stress activates all UPR sensors. However, survival is favored during mild stress as a consequence of the intrinsic instabilities of mRNAs and proteins that promote apoptosis compared to those that facilitate protein folding and adaptation. As a consequence, the expression of apoptotic proteins is short-lived as cells adapt to stress. We provide evidence that the selective persistence of ER chaperone expression is also applicable to at least one instance of genetic ER stress. This work provides new insight into how a stress response pathway can be structured to allow cells to avert death as they adapt. It underscores the contribution of posttranscriptional and posttranslational mechanisms in influencing this outcome.

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Crossref · 10.1371/journal.pbio.0040374

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Metadata

Authors
Rutkowski, D. T., Arnold, S. M., Miller, C. N., Wu, J., Li, J., Gunnison, K. M., Mori, K., Sadighi Akha, A. A., Raden, D., & Kaufman, R. J.
Venue
PLoS Biology
Published
2006-11-07
Volume
4
Issue
11
Pages
e374
ISSN
  • 1544-9173 (ISSN-L)
  • 1545-7885
OpenAlex
W1972482541
Cited by
800
References
6
FWCI
12.61
Type
journal article
Language
en
Open access
gold

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