title: Regulation of p97 in the ubiquitin-proteasome system by the UBX protein-family.
abstract: The AAA protein p97 is a central component in the ubiquitin-proteasome system, in which it is thought to act as a molecular chaperone, guiding protein substrates to the 26S proteasome for degradation. This function is dependent on association with cofactors that are specific to the different biological pathways p97 participates in. The UBX-protein family (ubiquitin regulatory X) constitutes the largest known group of p97 cofactors. We propose that the regulation of p97 by UBX-proteins utilizes conserved structural features of this family. Firstly, they act as scaffolding subunits in p97-containing multiprotein complexes, by providing additional interaction motifs. Secondly, they provide regulation of multiprotein complex assembly and we suggest two possible models for p97 substrate recruitment in the UPS pathway. Lastly, they impose constraints on p97 and its interaction with substrates and further cofactors. These features allow the regulation, within the UPS, of the competitive interactions on p97, a regulation that is crucial to allow the diverse functionality of p97.
authors.affiliation: Division of Molecular Biosciences, Centre for Structural Biology, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, UK.
authors.forename: Patrik
authors.initials: P
authors.lastname: Kloppsteck
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Ewens
authors.forename: Andreas
authors.initials: A
authors.lastname: Förster
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
authors.forename: Paul S
authors.initials: PS
authors.lastname: Freemont
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D040681:Structural Homology, Protein; D014452:Ubiquitins / Q000737:chemistry / Q000378:metabolism; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; D046912:Multiprotein Complexes; D014452:Ubiquitins; D000251:Adenosine Triphosphatases; D000074405:Valosin Containing Protein