The FAM104 proteins VCF1/2 promote the nuclear localization of p97/VCP

Abstract
Data availability
Article and author information
Metrics

Abstract

The ATPase p97 (also known as VCP, Cdc48) has crucial functions in a variety of important cellular processes such as protein quality control, organellar homeostasis and DNA damage repair, and its de-regulation is linked to neuro-muscular diseases and cancer. p97 is tightly controlled by numerous regulatory cofactors, but the full range and function of the p97-cofactor network is unknown. Here, we identify the hitherto uncharacterized FAM104 proteins as a conserved family of p97 interactors. The two human family members VCP nuclear cofactor family member 1 and 2 (VCF1/2) bind p97 directly via a novel, alpha-helical motif and associate with p97-UFD1-NPL4 and p97-UBXN2B complexes in cells. VCF1/2 localize to the nucleus and promote the nuclear import of p97. Loss of VCF1/2 results in reduced nuclear p97 levels, slow growth and hypersensitivity to chemical inhibition of p97 in the absence and presence of DNA damage, suggesting that FAM104 proteins are critical regulators of nuclear p97 functions.

Data availability

All data analysed during this study are included in the manuscript and supporting files; Source Data files will be made available before publication.

Article and author information

Author details

Maria Körner

Chair of Biochemistry I, University of Würzburg, Würzburg, Germany

Competing interests
The authors declare that no competing interests exist.
Susanne R Meyer

Chair of Biochemistry I, University of Würzburg, Würzburg, Germany

Competing interests
The authors declare that no competing interests exist.
Gabriella Marincola

Chair of Biochemistry I, University of Würzburg, Würzburg, Germany

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-9227-6554
Maximilian J Kern

Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Martinsried, Germany

Competing interests
The authors declare that no competing interests exist.
Clemens Grimm

Chair of Biochemistry I, University of Würzburg, Würzburg, Germany

Competing interests
The authors declare that no competing interests exist.
Christina Schuelein-Voelk

Core Unit High-Content Microscopy, University of Würzburg, Würzburg, Germany

Competing interests
The authors declare that no competing interests exist.
Utz Fischer

Chair of Biochemistry I, University of Würzburg, Würzburg, Germany

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-1465-6591
Kay Hofmann

Institute of Genetics, University of Cologne, Cologne, Germany

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-2289-9083
Alexander Buchberger

Chair of Biochemistry I,, University of Würzburg, Würzburg, Germany

For correspondence
alexander.buchberger@uni-wuerzburg.de

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-2836-0820

Funding

Deutsche Forschungsgemeinschaft (GRK2243/1+2)

Maria Körner

Deutsche Forschungsgemeinschaft (INST 93/1023-1-FUGG)

Christina Schuelein-Voelk

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.