Finding the will and the way of ERAD substrate retrotranslocation

Curr Opin Cell Biol. 2012 Aug;24(4):460-6. doi: 10.1016/ Epub 2012 Jul 30.


ER-associated degradation (ERAD) is a mechanism by which numerous ER-localized proteins are targeted for cytosolic degradation by the ubiquitin-proteasome system. A surprising and still-cryptic requirement of this process is the energy dependent retrotranslocation of both lumenal and membrane-embedded ER proteins into the cytosol for ongoing ubiquitination and proteasomal destruction. The current understanding, results, and open questions are discussed below for this intriguing and critical process of ERAD.

Publication types

  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cytosol / metabolism
  • Endoplasmic Reticulum / metabolism*
  • Endoplasmic Reticulum-Associated Degradation*
  • Humans
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Transport
  • Proteins / metabolism*
  • Ubiquitin / metabolism
  • Ubiquitination
  • Yeasts / metabolism


  • Proteins
  • Ubiquitin
  • Proteasome Endopeptidase Complex