Asymmetric arginine dimethylation determines life span in C. elegans by regulating forkhead transcription factor DAF-16.
Cell Metab
; 13(5): 505-16, 2011 May 04.
Article
em En
| MEDLINE
| ID: mdl-21531333
ABSTRACT
Arginine methylation is a widespread posttranslational modification of proteins catalyzed by a family of protein arginine methyltransferases (PRMTs). It is well established that PRMTs are implicated in various cellular processes, but their physiological roles remain unclear. Using nematodes with a loss-of-function mutation, we show that prmt-1, the major asymmetric arginine methyltransferase, is a positive regulator of longevity in C. elegans. This regulation is dependent on both its enzymatic activity and DAF-16/FoxO transcription factor, which is negatively regulated by AKT-mediated phosphorylation downstream of the DAF-2/insulin signaling. prmt-1 is also required for stress tolerance and fat storage but not dauer formation in daf-2 mutants. Biochemical analyses indicate that PRMT-1 methylates DAF-16, thereby blocking its phosphorylation by AKT. Disruption of PRMT-1 induces phosphorylation of DAF-16 with a concomitant reduction in the expression of longevity-related genes. Thus, we provide a mechanism by which asymmetric arginine dimethylation acts as an antiaging modification in C. elegans.
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Base de dados:
MEDLINE
Assunto principal:
Arginina
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Proteína-Arginina N-Metiltransferases
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Fatores de Transcrição
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Regulação da Expressão Gênica
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Caenorhabditis elegans
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Proteínas de Caenorhabditis elegans
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Longevidade
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Metilação
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article