Lysine methylation of VCP by a member of a novel human protein methyltransferase family.
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Kernstock S, Davydova E, Jakobsson M, Moen A, Pettersen S, Maelandsmo GM, Egge-Jacobsen W, Falnes PO
Lysine methylation of VCP by a member of a novel human protein methyltransferase family.
Nat Commun. 2012;3:1038. doi: 10.1038/ncomms2041.
- PubMed ID
- 22948820 [ View in PubMed]
- 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.