Lysine methylation of VCP by a member of a novel human protein methyltransferase family
(2012) In Nature Communications 3. p.1038-1038- 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... (More)
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.
(Less)
- author
- Kernstock, Stefan ; Davydova, Erna ; Jakobsson, Magnus LU ; Moen, Anders ; Pettersen, Solveig ; Mælandsmo, Gunhild M ; Egge-Jacobsen, Wolfgang and Falnes, Pål Ø
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Adenosine Triphosphatases/chemistry, Amino Acid Motifs, Amino Acid Sequence, Cell Cycle Proteins/chemistry, Cell Line, Humans, Lysine/metabolism, Methylation, Methyltransferases/genetics, Molecular Sequence Data, Multigene Family, Sequence Alignment, Valosin Containing Protein
- in
- Nature Communications
- volume
- 3
- pages
- 1038 - 1038
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:84867018639
- pmid:22948820
- ISSN
- 2041-1723
- DOI
- 10.1038/ncomms2041
- language
- English
- LU publication?
- no
- id
- 2326f35a-7992-4fae-b838-2913d16b48d8
- date added to LUP
- 2020-01-13 08:57:26
- date last changed
- 2024-07-24 12:34:24
@article{2326f35a-7992-4fae-b838-2913d16b48d8,
abstract = {{<p>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.</p>}},
author = {{Kernstock, Stefan and Davydova, Erna and Jakobsson, Magnus and Moen, Anders and Pettersen, Solveig and Mælandsmo, Gunhild M and Egge-Jacobsen, Wolfgang and Falnes, Pål Ø}},
issn = {{2041-1723}},
keywords = {{Adenosine Triphosphatases/chemistry; Amino Acid Motifs; Amino Acid Sequence; Cell Cycle Proteins/chemistry; Cell Line; Humans; Lysine/metabolism; Methylation; Methyltransferases/genetics; Molecular Sequence Data; Multigene Family; Sequence Alignment; Valosin Containing Protein}},
language = {{eng}},
pages = {{1038--1038}},
publisher = {{Nature Publishing Group}},
series = {{Nature Communications}},
title = {{Lysine methylation of VCP by a member of a novel human protein methyltransferase family}},
url = {{http://dx.doi.org/10.1038/ncomms2041}},
doi = {{10.1038/ncomms2041}},
volume = {{3}},
year = {{2012}},
}