2. Academic Validation
  3. The Unfolded Protein Response and Cell Fate Control

The Unfolded Protein Response and Cell Fate Control

  • Mol Cell. 2018 Jan 18;69(2):169-181. doi: 10.1016/j.molcel.2017.06.017.
Claudio Hetz 1,  Feroz R Papa 2
Affiliations

Affiliations

  • 1 Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile; Center for Geroscience, Brain Health and Metabolism, Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile; Buck Institute for Research on Aging, Novato, CA, USA; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA. Electronic address: [email protected].
  • 2 Department of Medicine, University of California, San Francisco, San Francisco, CA, USA; Department of Pathology, University of California, San Francisco, San Francisco, CA, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA, USA; Lung Biology Center, University of California, San Francisco, San Francisco, CA, USA; UCSF Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA, USA. Electronic address: [email protected].
PMID: 29107536 DOI: 10.1016/j.molcel.2017.06.017
Abstract

The secretory capacity of a cell is constantly challenged by physiological demands and pathological perturbations. To adjust and match the protein-folding capacity of the endoplasmic reticulum (ER) to changing secretory needs, cells employ a dynamic intracellular signaling pathway known as the unfolded protein response (UPR). Homeostatic activation of the UPR enforces adaptive programs that modulate and augment key aspects of the entire secretory pathway, whereas maladaptive UPR outputs trigger Apoptosis. Here, we discuss recent advances into how the UPR integrates information about the intensity and duration of ER stress stimuli in order to control cell fate. These findings are timely and significant because they inform an evolving mechanistic understanding of a wide variety of human diseases, including diabetes mellitus, neurodegeneration, and Cancer, thus opening up the potential for new therapeutic modalities to treat these diverse diseases.

Keywords

ATF6; ER stress; IRE1; PERK; UPR; apoptosis; proteostasis.

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