2011年5月
Asymmetric Arginine Dimethylation Determines Life Span in C. elegans by Regulating Forkhead Transcription Factor DAF-16
CELL METABOLISM
- 巻
- 13
- 号
- 5
- 開始ページ
- 505
- 終了ページ
- 516
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.cmet.2011.03.017
- 出版者・発行元
- CELL PRESS
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.
- リンク情報
- ID情報
-
- DOI : 10.1016/j.cmet.2011.03.017
- ISSN : 1550-4131
- PubMed ID : 21531333
- Web of Science ID : WOS:000290291300005