Control of p97 function by cofactor binding

FEBS Lett. 2015 Sep 14;589(19 Pt A):2578-89. doi: 10.1016/j.febslet.2015.08.028. Epub 2015 Aug 29.


p97 (also known as Cdc48, Ter94, and VCP) is an essential, abundant and highly conserved ATPase driving the turnover of ubiquitylated proteins in eukaryotes. Even though p97 is involved in highly diverse cellular pathways and processes, it exhibits hardly any substrate specificity on its own. Instead, it relies on a large number of regulatory cofactors controlling substrate specificity and turnover. The complexity as well as temporal and spatial regulation of the interactions between p97 and its cofactors is only beginning to be understood at the molecular level. Here, we give an overview on the structural framework of p97 interactions with its cofactors, the emerging principles underlying the assembly of complexes with different cofactors, and the pathogenic effects of disease-associated p97 mutations on cofactor binding.

Keywords: ATPases Associated with diverse cellular Activities; Inclusion Body Myopathy with Paget́s disease of the bone and Fronto-temporal Dementia; UBXD1; UFD1-NPL4; p47.

Publication types

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

MeSH terms

  • Adenosine Triphosphatases / chemistry*
  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism
  • Amino Acid Sequence
  • Cell Cycle Proteins / chemistry*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Protein Binding
  • Protein Structure, Tertiary*
  • Sequence Homology, Amino Acid
  • Substrate Specificity
  • Valosin Containing Protein


  • Cell Cycle Proteins
  • Adenosine Triphosphatases
  • VCP protein, human
  • Valosin Containing Protein