Apoptosis pp 191-204 | Cite as

Regulation of Apoptosis by the Unfolded Protein Response

  • Andrew Fribley
  • Kezhong Zhang
  • Randal J. KaufmanEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 559)


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.

Key words

Apoptosis Endoplasmic Reticulum Stress Unfolded Protein Response 



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


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Copyright information

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

Authors and Affiliations

  • Andrew Fribley
    • 1
  • Kezhong Zhang
    • 1
    • 2
  • Randal J. Kaufman
    • 1
    Email author
  1. 1.Department of Biological ChemistryThe University of Michigan Medical CenterAnn ArborUSA
  2. 2.Center for Molecular Medicine and GeneticsWayne State University School of MedicineDetroitUSA

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