Endoplasmic reticulum-associated protein degradation

Int Rev Cytol. 2003;223:39-81. doi: 10.1016/s0074-7696(05)23002-4.


Proteins that fail to fold properly as well as constitutive or regulated short-lived proteins of the endoplasmatic reticulum (ER) are subjected to proteolysis by cytosolic 26 S proteasomes. This process, termed ER-associated protein degradation (ERAD), has also been implicated in the generation of some important human disorders, for example, cystic fibrosis. To become accessible to the proteasome, ERAD substrates must first be retrogradely transported from the ER into the cytosol, in a process termed dislocation. Surprisingly, protein dislocation from the ER seems to require at least some components that also mediate import into this compartment. Moreover, polyubiquitination of ERAD substrates at the ER membrane as well as the cytoplasmic Cdc48p/Npl4p/Ufd1p complex were shown to contribute to this export reaction. In this article we will summarize our current knowledge on ERAD and discuss the possible function of certain components involved in this process.

Publication types

  • Review

MeSH terms

  • Animals
  • Cysteine Endopeptidases / metabolism*
  • Endoplasmic Reticulum / metabolism*
  • Humans
  • Multienzyme Complexes / metabolism*
  • Proteasome Endopeptidase Complex
  • Ubiquitin / metabolism


  • Multienzyme Complexes
  • Ubiquitin
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex