Protein dislocation from the ER requires polyubiquitination and the AAA-ATPase Cdc48

Nat Cell Biol. 2002 Feb;4(2):134-9. doi: 10.1038/ncb746.


Endoplasmic reticulum (ER)-associated protein degradation by the ubiquitin-proteasome system requires the dislocation of substrates from the ER into the cytosol. It has been speculated that a functional ubiquitin proteasome pathway is not only essential for proteolysis, but also for the preceding export step. Here, we show that short ubiquitin chains synthesized on proteolytic substrates are not sufficient to complete dislocation; the size of the chain seems to be a critical determinant. Moreover, our results suggest that the AAA proteins of the 26S proteasome are not directly involved in substrate export. Instead, a related AAA complex Cdc48, is required for ER-associated protein degradation upstream of the proteasome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / metabolism*
  • Carboxypeptidases / genetics
  • Carboxypeptidases / metabolism
  • Cathepsin A
  • Cell Cycle Proteins / metabolism*
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism
  • Endoplasmic Reticulum / metabolism*
  • Fungal Proteins / metabolism
  • Molecular Weight
  • Nuclear Pore Complex Proteins*
  • Nuclear Proteins / metabolism
  • Nucleocytoplasmic Transport Proteins
  • Peptide Hydrolases / metabolism
  • Proteasome Endopeptidase Complex*
  • Protein Transport / physiology*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Ubiquitin / metabolism*
  • Valosin Containing Protein
  • Vesicular Transport Proteins


  • Cell Cycle Proteins
  • Fungal Proteins
  • NPL4 protein, S cerevisiae
  • Nuclear Pore Complex Proteins
  • Nuclear Proteins
  • Nucleocytoplasmic Transport Proteins
  • Saccharomyces cerevisiae Proteins
  • UFD1 protein, S cerevisiae
  • Ubiquitin
  • Vesicular Transport Proteins
  • Carboxypeptidases
  • Peptide Hydrolases
  • Cathepsin A
  • Proteasome Endopeptidase Complex
  • ATP dependent 26S protease
  • Adenosine Triphosphatases
  • CDC48 protein, S cerevisiae
  • Valosin Containing Protein