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Regulation of Apoptosis by the Unfolded Protein Response

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Apoptosis

Part of the book series: Methods in Molecular Biology ((MIMB,volume 559))

Summary

In eukaryotic cells, the endoplasmic reticulum (ER) serves many specialized functions including bio-synthesis and assembly of membrane and secretory proteins, calcium storage and production of lipids and sterols. As a plant for protein folding and posttranslational modification, the ER provides stringent quality control systems to ensure that only correctly folded proteins exit the ER and unfolded or misfolded proteins are retained and ultimately degraded. Biochemical, physiological, and pathological stimuli that interfere with ER function can disrupt ER homeostasis, impose stress to the ER, and subsequently cause accumulation of unfolded or misfolded proteins in the ER lumen. To deal with accumulation of unfolded or misfolded proteins, the cell has evolved highly specific signaling pathways collectively called the “unfolded protein response” (UPR) to restore normal ER functions. However, if the overload of unfolded or misfolded proteins in the ER is not resolved, the prolonged UPR will induce ER stress-associated programmed cell death, apoptosis, to protect the organism by removing the stressed cells. In this chapter, we summarize our current understanding of UPR-induced apoptosis and various methods to detect ER stress and apoptosis in mammalian cells.

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Acknowledgments

Portions of this work were supported by NIH grants DK042394, HL052173, and HL057346. RJK is an Investigator of the Howard Hughes Medical Institute.

Author information

Authors and Affiliations

  1. Department of Biological Chemistry, The University of Michigan Medical Center, Ann Arbor, MI, USA

    Andrew Fribley, Kezhong Zhang & Randal J. Kaufman

  2. Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, USA

    Kezhong Zhang

Authors
  1. Andrew Fribley
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  2. Kezhong Zhang
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  3. Randal J. Kaufman
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Corresponding author

Correspondence to Randal J. Kaufman .

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Editors and Affiliations

  1. Boston Biomedical Research Institute, Grove Street 64, Watertown, 02472, U.S.A.

    Peter Erhardt

  2. Boston Biomedical Research Institute, Grove Street 64, Watertown, 02472, U.S.A.

    Ambrus Toth

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© 2009 Humana Press, a part of Springer Science+Business Media, LLC

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Fribley, A., Zhang, K., Kaufman, R.J. (2009). Regulation of Apoptosis by the Unfolded Protein Response. In: Erhardt, P., Toth, A. (eds) Apoptosis. Methods in Molecular Biology, vol 559. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-017-5_14

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  • DOI: https://doi.org/10.1007/978-1-60327-017-5_14

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60327-016-8

  • Online ISBN: 978-1-60327-017-5

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