ヒロタ　ケイコ   Keiko HIROTA   廣田　恵子    所属   医学部 医学科    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Asymmetric arginine dimethylation determines lifespan in C. elegans by regulating forkhead transcription factor DAF-16
掲載誌名	正式名：Cell metabolism 略　 称：Cell Metab ISSNコード：15504131
掲載区分	国外
巻・号・頁	13(5),pp.505-516
著者・共著者	TAKAHASHI Yuta†, DAITOKU Hiroaki, HIROTA Keiko, TAMIYA Hiroko, YOKOYAMA Atsuko, KAKO Koichiro, NAGASHIMA Yusuke, NAKAMURA Ayumi, SHIMADA Takashi, WATANABE Satoshi, YAMAGATA Kazuyuki, YASUDA Kayo, ISHII Naoaki, FUKAMIZU Akiyoshi*
発行年月	2011/05
概要	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.
DOI	10.1016/j.cmet.2011.03.017.