※ をクリックすると外部の論文のサイトが開きます。
論文
- タイトル
- タイトル（英）
- mTOR-AKT Signaling in Cellular Clock Resetting Triggered by Osmotic Stress.
- 参照URL
- https://researchmap.jp/Yoshitane/published_papers/36605005
- 著者
- 著者（英）
- Hikari Yoshitane,Kiyomichi Imamura,Takenori Okubo,Yuta Otobe,Satoshi Kawakami,Shunsuke Ito,Toru Takumi,Kazuki Hattori,Isao Naguro,Hidenori Ichijo,Yoshitaka Fukada
- 担当区分
- 概要
- 概要（英）
- Aims: The circadian clock oscillates in a cell-autonomous manner with a period of ∼24 h, and the phase is regulated by various time cues such as light and temperature through multiple clock input pathways. We previously found that osmotic and oxidative stress strongly affected the circadian period and phase of cellular rhythms, and triple knockout of apoptosis signal-regulating kinase (ASK) family members, Ask1, Ask2, and Ask3, abolished the phase shift (clock resetting) induced by hyperosmotic pulse treatment. We aimed at exploring a key molecule(s) and signaling events in the clock input pathway dependent on ASK kinases. Results: The phase shift of the cellular clock induced by the hyperosmotic pulse treatment was significantly reduced by combined deficiencies of the clock(-related) genes, Dec1, Dec2, and E4 promoter-binding protein 4 (also known as Nfil3) (E4bp4). In addition, liquid chromatography mass/mass spectrometry (LC-MS/MS)-based proteomic analysis identified hyperosmotic pulse-induced phosphorylation of circadian locomotor output cycles caput (CLOCK) Ser845 in an AKT-dependent manner. We found that AKT kinase was phosphorylated at Ser473 (i.e., activated) in response to the hyperosmotic pulse experiments. Inhibition of mechanistic target of rapamycin (mTOR) kinase by Torin 1 treatment completely abolished the AKT activation, suppressed the phosphorylation of CLOCK Ser845, and blocked the clock resetting induced by the hyperosmotic pulse treatment. Innovation and Conclusions: We conclude that mTOR-AKT signaling is indispensable for the CLOCK Ser845 phosphorylation, which correlates with the clock resetting induced by the hyperosmotic pulse treatment. Immediate early induction of the clock(-related) genes and CLOCK carboxyl-terminal (C-terminal) region containing Ser845 also play important roles in the clock input pathway through redox-sensitive ASK kinases.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 誌名（英）
- Antioxidants & redox signaling
- 巻
- 号
- 開始ページ
- 終了ページ
- 出版年月
- 2022年3月18日
- 査読の有無
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- DOI URL
- https://doi.org/10.1089/ars.2021.0059
- 共同研究・競争的資金等の研究課題
研究者
吉種 光
(ヨシタネ ヒカリ)