論文 - 詳細
RRC ID | 46515 |
---|---|
著者 | Takahashi Y, Daitoku H, Hirota K, Tamiya H, Yokoyama A, Kako K, Nagashima Y, Nakamura A, Shimada T, Watanabe S, Yamagata K, Yasuda K, Ishii N, Fukamizu A. |
タイトル | Asymmetric arginine dimethylation determines life span in C. elegans by regulating forkhead transcription factor DAF-16. |
ジャーナル | Cell Metab |
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. |
巻・号 | 13(5) |
ページ | 505-16 |
公開日 | 2011-5-4 |
DOI | 10.1016/j.cmet.2011.03.017 |
PII | S1550-4131(11)00141-0 |
PMID | 21531333 |
MeSH | Amino Acid Sequence Animals Arginine / genetics* Arginine / metabolism Blotting, Western Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Forkhead Transcription Factors / genetics Forkhead Transcription Factors / metabolism Gene Expression Regulation* Immunoprecipitation Insulin / genetics Insulin / metabolism Longevity / genetics* Methylation* Molecular Sequence Data Mutation / genetics Phosphorylation Polymerase Chain Reaction Protein-Arginine N-Methyltransferases / genetics Protein-Arginine N-Methyltransferases / metabolism* Proto-Oncogene Proteins c-akt / genetics Proto-Oncogene Proteins c-akt / metabolism Receptor, Insulin / genetics Receptor, Insulin / metabolism Sequence Homology, Amino Acid Signal Transduction Transcription Factors / genetics Transcription Factors / metabolism* |
IF | 21.567 |
引用数 | 49 |
WOS 分野 | ENDOCRINOLOGY & METABOLISM CELL BIOLOGY |
リソース情報 | |
線虫 | tm3613 |