Mechanisms, regulation and functions of the unfolded protein response

  • Nat Rev Mol Cell Biol. 2020 Aug;21(8):421-438. doi: 10.1038/s41580-020-0250-z.
Claudio Hetz  1  2  3  4 ,  Kezhong Zhang  5  6 ,  Randal J Kaufman  7
Affiliations
  • 1. Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile. [email protected].
  • 2. FONDAP Center for Geroscience Brain Health and Metabolism (GERO), Santiago, Chile. [email protected].
  • 3. Program of Cellular and Molecular Biology, Institute of Biomedical Science, University of Chile, Santiago, Chile. [email protected].
  • 4. Buck Institute for Research on Aging, Novato, CA, USA. [email protected].
  • 5. Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, USA. [email protected].
  • 6. Department of Biochemistry, Microbiology and Immunology, Wayne State University School of Medicine, Detroit, MI, USA. [email protected].
  • 7. Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA. [email protected].
PMID: 32457508 DOI: 10.1038/s41580-020-0250-z
Abstract

Cellular stress induced by the abnormal accumulation of unfolded or misfolded proteins at the endoplasmic reticulum (ER) is emerging as a possible driver of human diseases, including Cancer, diabetes, Obesity and neurodegeneration. ER proteostasis surveillance is mediated by the unfolded protein response (UPR), a signal transduction pathway that senses the fidelity of protein folding in the ER lumen. The UPR transmits information about protein folding status to the nucleus and cytosol to adjust the protein folding capacity of the cell or, in the event of chronic damage, induce apoptotic cell death. Recent advances in the understanding of the regulation of UPR signalling and its implications in the pathophysiology of disease might open new therapeutic avenues.