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Recruitment of the p97 ATPase and ubiquitin ligases to the site of retrotranslocation at the endoplasmic reticulum membrane.

http://www.ncbi.nlm.nih.gov/pubmed/16186510

Misfolded proteins are eliminated from the endoplasmic reticulum (ER) by retrotranslocation into the cytosol, a pathway hijacked by certain viruses to destroy MHC class I heavy chains. The translocation of polypeptides across the ER membrane requires their polyubiquitination and subsequent extraction from the membrane by the p97 ATPase [also called valosin-containing protein (VCP) or, in yeast, Cdc48]. In higher eukaryotes, p97 is bound to the ER membrane by a membrane protein complex containing Derlin-1 and VCP-interacting membrane protein (VIMP). How the ubiquitination machinery is recruited to the p97/Derlin/VIMP complex is unclear. Here, we report that p97 interacts directly with several ubiquitin ligases and facilitates their recruitment to Derlin-1. During retrotranslocation, a substrate first interacts with Derlin-1 before p97 and other factors join the complex. These data, together with the fact that Derlin-1 is a multispanning membrane protein forming homo-oligomers, support the idea that Derlin-1 is part of a retrotranslocation channel that is associated with both the polyubiquitination and p97-ATPase machineries.

Pubmed ID: 16186510 RIS Download

Mesh terms: Adenosine Triphosphatases | Endoplasmic Reticulum | Fluorescent Antibody Technique | HeLa Cells | Humans | Immunoprecipitation | Membrane Proteins | Models, Molecular | Multiprotein Complexes | Nuclear Proteins | Peptide Fragments | Protein Folding | Protein Transport | Selenoproteins | Ubiquitin-Protein Ligases

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Associated grants

  • Agency: NIGMS NIH HHS, Id: R01 GM05586-10

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