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. Epub 2020 May 26.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Endoplasmic Reticulum / metabolism
  • Endoplasmic Reticulum / physiology
  • Endoplasmic Reticulum Stress / physiology*
  • Humans
  • Neoplasms / metabolism
  • Protein Folding
  • Proteins / metabolism
  • Signal Transduction
  • Unfolded Protein Response / genetics*
  • Unfolded Protein Response / physiology*


  • Proteins