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