| First Author | Kernstock S | Year | 2012 |
| Journal | Nat Commun | Volume | 3 |
| Pages | 1038 | PubMed ID | 22948820 |
| Mgi Jnum | J:192765 | Mgi Id | MGI:5466455 |
| Doi | 10.1038/ncomms2041 | Citation | Kernstock S, et al. (2012) Lysine methylation of VCP by a member of a novel human protein methyltransferase family. Nat Commun 3:1038 |
| abstractText | 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. |
