title: VCP and PSMF1: Antagonistic regulators of proteasome activity.
abstract: Protein turnover and quality control by the proteasome is of paramount importance for cell homeostasis. Dysfunction of the proteasome is associated with aging processes and human diseases such as neurodegeneration, cardiomyopathy, and cancer. The regulation, i.e. activation and inhibition of this fundamentally important protein degradation system, is still widely unexplored. We demonstrate here that the evolutionarily highly conserved type II triple-A ATPase VCP and the proteasome inhibitor PSMF1/PI31 interact directly, and antagonistically regulate proteasomal activity. Our data provide novel insights into the regulation of proteasomal activity.
authors.affiliation: Institute of Biochemistry I, Medical Faculty, University of Cologne, 50931 Cologne, Germany. Electronic address: christoph.clemen@uni-koeln.de.
authors.forename: Christoph S
authors.initials: CS
authors.lastname: Clemen
authors.affiliation: Institute of Biochemistry I, Medical Faculty, University of Cologne, 50931 Cologne, Germany.
authors.forename: Marija
authors.initials: M
authors.lastname: Marko
authors.affiliation: Institute of Biochemistry I, Medical Faculty, University of Cologne, 50931 Cologne, Germany.
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Strucksberg
authors.affiliation: Institute of Biochemistry I, Medical Faculty, University of Cologne, 50931 Cologne, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Behrens
authors.affiliation: Functional Proteomics, SFB815 Core Unit, Medical Faculty, Goethe University, 60590 Frankfurt, Germany.
authors.forename: Ilka
authors.initials: I
authors.lastname: Wittig
authors.affiliation: Molecular Cardiology, Department of Internal Medicine II, University Hospital Ulm, 89081 Ulm, Germany.
authors.forename: Linda
authors.initials: L
authors.lastname: Gärtner
authors.affiliation: Institute of Neuropathology, University Hospital Erlangen, 91054 Erlangen, Germany.
authors.forename: Lilli
authors.initials: L
authors.lastname: Winter
authors.affiliation: Institute of Neuropathology, University Hospital Erlangen, 91054 Erlangen, Germany.
authors.forename: Frederic
authors.initials: F
authors.lastname: Chevessier
authors.affiliation: Institute of Biochemistry I, Medical Faculty, University of Cologne, 50931 Cologne, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Matthias
authors.affiliation: Department of Neurology, University Hospital Erlangen, 91054 Erlangen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Türk
authors.affiliation: Institute of Biochemistry I, Medical Faculty, University of Cologne, 50931 Cologne, Germany.
authors.forename: Karthikeyan
authors.initials: K
authors.lastname: Tangavelou
authors.affiliation: Institute of Neuropathology, University Hospital Erlangen, 91054 Erlangen, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Schütz
authors.affiliation: Institute of Biochemistry I, Medical Faculty, University of Cologne, 50931 Cologne, Germany.
authors.forename: Khalid
authors.initials: K
authors.lastname: Arhzaouy
authors.affiliation: Institute of Genetics, University of Cologne, 50674 Cologne, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Klopffleisch
authors.affiliation: Institute of Biochemistry II, Medical Faculty, and Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany.
authors.forename: Franz-Georg
authors.initials: FG
authors.lastname: Hanisch
authors.affiliation: Molecular Cardiology, Department of Internal Medicine II, University Hospital Ulm, 89081 Ulm, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rottbauer
authors.affiliation: Institute of Neuropathology, University Hospital Erlangen, 91054 Erlangen, Germany.
authors.forename: Ingmar
authors.initials: I
authors.lastname: Blümcke
authors.affiliation: Molecular Cardiology, Department of Internal Medicine II, University Hospital Ulm, 89081 Ulm, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Just
authors.affiliation: Institute of Biochemistry I, Medical Faculty, University of Cologne, 50931 Cologne, Germany.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Eichinger
authors.affiliation: Structural Chemistry Program, Eskitis Institute, Griffith University, Queensland 4111, Australia; Faculty of Veterinary Science, The University of Melbourne, Victoria 3030, Australia.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hofmann
authors.affiliation: Institute of Neuropathology, University Hospital Erlangen, 91054 Erlangen, Germany. Electronic address: rolf.schroeder@uk-erlangen.de.
authors.forename: Rolf
authors.initials: R
authors.lastname: Schröder
mesh_terms: D000251:Adenosine Triphosphatases / Q000502:physiology*; D001704:Biopolymers; D018797:Cell Cycle Proteins / Q000502:physiology*; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000502:physiology*; D011506:Proteins / Q000502:physiology*; D000074405:Valosin Containing Protein
chemical_list: D001704:Biopolymers; D018797:Cell Cycle Proteins; C121623:PSMF1 protein, human; D011506:Proteins; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein; C000614179:Vcp protein, mouse
keywords: Dictyostelium discoideum; Mouse model; PSMF1; Proteasome; Proteasome inhibitor PI31; Protein quality control; Regulation; Triple-A ATPase; VCP; p97