Emerging functions of the VCP/p97 AAA-ATPase in the ubiquitin system

Nat Cell Biol. 2012 Feb 2;14(2):117-23. doi: 10.1038/ncb2407.


The ATP-driven chaperone valosin-containing protein (VCP)/p97 governs critical steps in ubiquitin-dependent protein quality control and intracellular signalling pathways. It cooperates with diverse partner proteins to help process ubiquitin-labelled proteins for recycling or degradation by the proteasome in many cellular contexts. Recent studies have uncovered unexpected cellular functions for p97 in autophagy, endosomal sorting and regulating protein degradation at the outer mitochondrial membrane, and elucidated a role for p97 in key chromatin-associated processes. These findings extend the functional relevance of p97 to lysosomal degradation and reveal a surprising dual role in protecting cells from protein stress and ensuring genome stability during proliferation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism*
  • Autophagy
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Endosomes / metabolism
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Mutation
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Processing, Post-Translational*
  • Proteolysis
  • Ubiquitin / metabolism*
  • Valosin Containing Protein


  • Cell Cycle Proteins
  • Ubiquitin
  • Proteasome Endopeptidase Complex
  • Adenosine Triphosphatases
  • VCP protein, human
  • Valosin Containing Protein