VCP and PSMF1: Antagonistic regulators of proteasome activity

Christoph S Clemen; Marija Marko; Karl-Heinz Strucksberg; Juliane Behrens; Ilka Wittig; Linda Gärtner; Lilli Winter; Frederic Chevessier; Jan Matthias; Matthias Türk; Karthikeyan Tangavelou; Johanna Schütz; Khalid Arhzaouy; Karsten Klopffleisch; Franz-Georg Hanisch; Wolfgang Rottbauer; Ingmar Blümcke; Steffen Just; Ludwig Eichinger; Andreas Hofmann; Rolf Schröder

doi:10.1016/j.bbrc.2015.06.086

VCP and PSMF1: Antagonistic regulators of proteasome activity

Biochem Biophys Res Commun. 2015 Aug 7;463(4):1210-7. doi: 10.1016/j.bbrc.2015.06.086. Epub 2015 Jun 15.

Authors

Christoph S Clemen¹, Marija Marko², Karl-Heinz Strucksberg², Juliane Behrens², Ilka Wittig³, Linda Gärtner⁴, Lilli Winter⁵, Frederic Chevessier⁵, Jan Matthias², Matthias Türk⁶, Karthikeyan Tangavelou², Johanna Schütz⁵, Khalid Arhzaouy², Karsten Klopffleisch⁷, Franz-Georg Hanisch⁸, Wolfgang Rottbauer⁴, Ingmar Blümcke⁵, Steffen Just⁴, Ludwig Eichinger², Andreas Hofmann⁹, Rolf Schröder¹⁰

Affiliations

¹ Institute of Biochemistry I, Medical Faculty, University of Cologne, 50931 Cologne, Germany. Electronic address: [email protected].
² Institute of Biochemistry I, Medical Faculty, University of Cologne, 50931 Cologne, Germany.
³ Functional Proteomics, SFB815 Core Unit, Medical Faculty, Goethe University, 60590 Frankfurt, Germany.
⁴ Molecular Cardiology, Department of Internal Medicine II, University Hospital Ulm, 89081 Ulm, Germany.
⁵ Institute of Neuropathology, University Hospital Erlangen, 91054 Erlangen, Germany.
⁶ Department of Neurology, University Hospital Erlangen, 91054 Erlangen, Germany.
⁷ Institute of Genetics, University of Cologne, 50674 Cologne, Germany.
⁸ Institute of Biochemistry II, Medical Faculty, and Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany.
⁹ Structural Chemistry Program, Eskitis Institute, Griffith University, Queensland 4111, Australia; Faculty of Veterinary Science, The University of Melbourne, Victoria 3030, Australia.
¹⁰ Institute of Neuropathology, University Hospital Erlangen, 91054 Erlangen, Germany. Electronic address: [email protected].

PMID: 26086101
DOI: 10.1016/j.bbrc.2015.06.086

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.

Keywords: Dictyostelium discoideum; Mouse model; PSMF1; Proteasome; Proteasome inhibitor PI31; Protein quality control; Regulation; Triple-A ATPase; VCP; p97.

Publication types

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

MeSH terms

Adenosine Triphosphatases / physiology*
Biopolymers
Cell Cycle Proteins / physiology*
Humans
Proteasome Endopeptidase Complex / physiology*
Proteins / physiology*
Valosin Containing Protein

Substances

Biopolymers
Cell Cycle Proteins
PSMF1 protein, human
Proteins
Proteasome Endopeptidase Complex
Adenosine Triphosphatases
VCP protein, human
Valosin Containing Protein
Vcp protein, mouse