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  • Review Article
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Proteostasis control by the unfolded protein response

Nature Cell Biology volume 17, pages 829–838 (2015)Cite this article

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An Erratum to this article was published on 31 July 2015

This article has been updated

Abstract

Stress induced by accumulation of misfolded proteins in the endoplasmic reticulum is observed in many physiological and pathological conditions. To cope with endoplasmic reticulum stress, cells activate the unfolded protein response, a dynamic signalling network that orchestrates the recovery of homeostasis or triggers apoptosis, depending on the level of damage. Here we provide an overview of recent insights into the mechanisms that cells employ to maintain proteostasis and how the unfolded protein response determines cell fate under endoplasmic reticulum stress.

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Figure 1: The three arms of the UPR.
Figure 2: Under irremediable ER stress, the UPR actively promotes proteotoxicity, inflammatory responses and apoptosis.
Figure 3: The UPRosome: fine-tuning ER stress signalling through protein–protein interactions and/or post-translational modifications.
Figure 4: ER stress-independent functions of the UPR.

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Change history

  • 13 July 2015

    In the version of this Review originally published, Fig. 1 contained a superfluous IRE1α stress sensor at the top of the schematic. This error has been corrected in all online versions.

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Acknowledgements

We thank Hery Urra and Victor Hugo Cornejo for figure design. Funded by ECOS-CONICYT C13S02 (C.H., E.C.), Ring Initiative-ACT1109, FONDEF-D11I1007, Millennium Institute-P09-015-F, the Frick Foundation, FONDECYT no. 1140549, Michael J. Fox Foundation for Parkinson Research, COPEC-UC Foundation, CONICYT grant USA2013-0003 (C.H.), the Institut National du Cancer (PLBio and ICGC; INCa) and La Ligue Nationale Contre le Cancer (LARGE) (E.C.); NIH: RO1CA136577 and R01-DK095306, American Cancer Society Research Scholar Award, Harrington Discovery Institute Scholar-Innovator Award, Michael J. Fox Foundation for Parkinson's Research, Caring for Carcinoid Foundation and American Association for Cancer Research (S.A.O.).

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Authors and Affiliations

  1. Chile; and in the Department of Immunology and Infectious Diseases, Claudio Hetz is at the Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile; the Institute of Biomedical Sciences (ICBM), Program of Cellular and Molecular Biology, Center for Molecular Studies of the Cell, University of Chile, Santiago, Harvard School of Public Health, Boston, Massachusetts 02115, USA,

    Claudio Hetz

  2. the Institute of Biomedical Sciences (ICBM), Program of Cellular and Molecular Biology, Center for Molecular Studies of the Cell, University of Chile, Santiago, Chile,

    Claudio Hetz

  3. Eric Chevet is at ER440, Oncogenesis, stress and signaling, University of Rennes 1, 35000 Rennes, France,

    Eric Chevet

  4. the Centre Régional de Lutte Contre le Cancer Eugène Marquis, 35000 Rennes, France,

    Eric Chevet

  5. Scott A. Oakes is in the Department of Pathology, Diabetes Center, and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California 94143, USA,

    Scott A. Oakes

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  1. Claudio Hetz
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Correspondence to Claudio Hetz, Eric Chevet or Scott A. Oakes.

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Hetz, C., Chevet, E. & Oakes, S. Proteostasis control by the unfolded protein response. Nat Cell Biol 17, 829–838 (2015). https://doi.org/10.1038/ncb3184

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