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Lysine methylation of VCP by a member of a novel human protein methyltransferase family

Author

Listed:
  • Stefan Kernstock

    (Faculty of Mathematics and Natural Sciences, University of Oslo)

  • Erna Davydova

    (Faculty of Mathematics and Natural Sciences, University of Oslo)

  • Magnus Jakobsson

    (Faculty of Mathematics and Natural Sciences, University of Oslo)

  • Anders Moen

    (Glyconor Mass Spectrometry, Faculty of Mathematics and Natural Sciences, University of Oslo)

  • Solveig Pettersen

    (Institute for Cancer Research, the Norwegian Radium Hospital, Oslo University Hospital)

  • Gunhild M. Mælandsmo

    (Institute for Cancer Research, the Norwegian Radium Hospital, Oslo University Hospital)

  • Wolfgang Egge-Jacobsen

    (Glyconor Mass Spectrometry, Faculty of Mathematics and Natural Sciences, University of Oslo)

  • Pål Ø. Falnes

    (Faculty of Mathematics and Natural Sciences, University of Oslo)

Abstract

Valosin-containing protein (VCP, also called p97) is an essential and highly conserved adenosine triphosphate-dependent chaperone implicated in a wide range of cellular processes in eukaryotes, and mild VCP mutations can cause severe neurodegenerative disease. Here we show that mammalian VCP is trimethylated on Lys315 in a variety of cell lines and tissues, and that the previously uncharacterized protein METTL21D (denoted here as VCP lysine methyltransferase, VCP-KMT) is the responsible enzyme. VCP methylation was abolished in three human VCP-KMT knockout cell lines generated with zinc-finger nucleases. Interestingly, VCP-KMT was recently reported to promote tumour metastasis, and indeed, VCP-KMT-deficient cells displayed reduced growth rate, migration and invasive potential. Finally, we present data indicating that VCP-KMT, calmodulin-lysine methyltransferase and eight uncharacterized proteins together constitute a novel human protein methyltransferase family. The present work provides new insights on protein methylation and its links to human disease.

Suggested Citation

  • Stefan Kernstock & Erna Davydova & Magnus Jakobsson & Anders Moen & Solveig Pettersen & Gunhild M. Mælandsmo & Wolfgang Egge-Jacobsen & Pål Ø. Falnes, 2012. "Lysine methylation of VCP by a member of a novel human protein methyltransferase family," Nature Communications, Nature, vol. 3(1), pages 1-11, January.
    • Handle: RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms2041
    DOI: 10.1038/ncomms2041
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