Signal transduction from the endoplasmic reticulum to the cell nucleus

Physiol Rev. 1999 Jul;79(3):683-701. doi: 10.1152/physrev.1999.79.3.683.


The endoplasmic reticulum (ER) serves several important functions. Cholesterol, an essential component of cellular membranes, is synthesized on the ER surface. Inside the organelle, proteins destined for secretion or transport to the cell surface are folded and become glycosylated. Because these processes are essential for cell viability, a disturbance in ER function presents significant stress to the cell. In response to ER stress, three distinct signal transduction pathways can be activated. Two of these, the unfolded protein response and the ER-overload response, respond to disturbances in protein processing. The third, the sterol regulatory cascade, is activated by depletion of cholesterol. This review summarizes the recent advances in our understanding of these ER-nuclear signal transduction pathways. In addition, it points to novel regulatory mechanisms discovered in these pathways, which may be widely used in other systems.

Publication types

  • Review

MeSH terms

  • Animals
  • CCAAT-Enhancer-Binding Proteins*
  • Cell Nucleus / physiology*
  • DNA-Binding Proteins / physiology
  • Endoplasmic Reticulum / physiology*
  • NF-kappa B / physiology
  • Nuclear Proteins / physiology
  • Signal Transduction / physiology*
  • Sterol Regulatory Element Binding Protein 1
  • Transcription Factors*


  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins
  • NF-kappa B
  • Nuclear Proteins
  • Sterol Regulatory Element Binding Protein 1
  • Transcription Factors