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Nat Commun. 2012;3:1038. doi: 10.1038/ncomms2041.

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

Author information

1
Department of Molecular Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo 0316 Norway.

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.

PMID:
22948820
DOI:
10.1038/ncomms2041
[Indexed for MEDLINE]

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