A genome-wide RNAi screening for clarifying the molecular mechanism of osmotic stress response in the mammalian cell

• Project/Area Number: 25650004
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Molecular biology
• Research Institution: The University of Tokyo
• Principal Investigator: NAGURO Isao 東京大学, 薬学研究科(研究院), 講師 (80401222)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ASK3 / 浸透圧 / RNAiスクリーニング / MAPK / キナーゼ / ハイコンテントアナリシス

Outline of Final Research Achievements

We studied the molecular mechanism how mammalian cells sense and transduce osmotic stress information, using ASK3 as an original probe. According to the results obtained from genome-wide siRNA screenings for ASK3 regulators, it is suggested that hypo- and hyper-tonic stress are received by different system. Moreover, we found that an unexpected molecule is involved in the signal transduction of hypertonic stress.
Our results contribute to the comprehensive understanding of osmotic stress response in the mammalian cells and blood pressure regulation, which is closely related to the osmotic stress-responsive molecules such as ASK3.

Research Products

• [Journal Article] Apoptosis Signal-regulating Kinase 1(ASK1)-p38 pathway-dependent cytoplasmic translocation of the orphan nuclear receptor NR4A2 is required for oxidative stress-induced necrosis (2015)
  • Author(s): Watanabe T, Sekine S, Naguro I, Sekine Y, Ichijo H.
  • Journal Title: J Biol Chem Volume: in press Issue: 17 Pages: 10791-10803
  • DOI: 10.1074/jbc.m114.623280
  • NAID: 120007150218
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The DEAH-Box RNA Helicase DHX15 activates NF-κB and MAPK signaling downstream of MAVS during antiviral responses (2014)
  • Author(s): Mosallanejad, K., Sekine, Y., Ishikura-Kinoshita, S., Kumagai, K., Nagano, T., Matsuzawa, A., Takeda, K., Naguro, I. and Ichijo, H.
  • Journal Title: Sci. Signal. Volume: 7 Issue: 323
  • DOI: 10.1126/scisignal.2004841
  • Peer Reviewed
• [Journal Article] Apoptosis Signal-Regulating Kinase 1 (ASK1) as a therapeutic target (2014)
  • Author(s): Kawarazaki, Y., Ichijo, H. and Naguro, I.
  • Journal Title: Expert Opinion on Therapeutic Targets Volume: 18 Issue: 6 Pages: 651-664
  • DOI: 10.1517/14728222.2014.896903
  • Peer Reviewed
• [Journal Article] Roquin-2 promotes ubiquitin-mediated degradation of ASK1 to regulate stress responses (2014)
  • Author(s): Maruyama, T., Araki, T., Kawarazaki, Y., Naguro, I., Heynen, S., Aza-Blanc, P., Ronai, Z., Matsuzawa, A. and Ichijo, H.
  • Journal Title: Sci. Signal. Volume: 7 Issue: 309
  • DOI: 10.1126/scisignal.2004822
  • Peer Reviewed / Open Access
• [Journal Article] SOD1 as a molecular switch for initiating the homeostatic ER stress respouse under zinc deficiency. (2013)
  • Author(s): Homma, K., Fujisawa. T., Tsuburaya, N., Yamaguchi, N., Kadowaki, H., Takeda, K., Nishitoh, H., Matsuzawa, A., Naguro, I., and Ichijo, H.
  • Journal Title: Molecular Cell Volume: 52 Issue: 1 Pages: 75-86
  • DOI: 10.1016/j.molcel.2013.08.038
  • Peer Reviewed
• [Presentation] ストレス応答性キナーゼASKファミリータンパク質の疾患への関わりと活性制御機構 (2014)
  • Author(s): 名黒 功、一條 秀憲
  • Organizer: 日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2014-10-18
  • Invited
• [Presentation] Oxidative stress-activated kinase ASK1 is involved in the tumorigenesis and tumor metastasis (2014)
  • Author(s): Isao Naguro, Miki Kamiyama, Hidenori Ichijo
  • Organizer: Gordon Research Conference Tiol-Based Redox Regulation & Signaling
  • Place of Presentation: Girona, Spain
  • Year and Date: 2014-07-20 – 2014-07-25
• [Presentation] Genome-wide siRNA screening for regulators of the osmotic stress-responsive kinase (2013)
  • Author(s): Isao Naguro, Kengo Watanabe, Hidenori Ichijo
  • Organizer: Discovery on Target Functional Genomics Screening Strategies
  • Place of Presentation: Boston U.S.A.
• [Presentation] 浸透圧ストレスに両方向性に応答するASK3の役割 (2013)
  • Author(s): 名黒 功、一條 秀憲
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 神奈川県横浜市
• [Presentation] 浸透圧ストレスに応答するキナーゼASK3を介する細胞体積と血圧の調節 (2013)
  • Author(s): 名黒 功、一條 秀憲
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 兵庫県神戸市
• [Remarks] 東京大学 大学院薬学系研究科 細胞情報学教室
  • URL: http://www.f.u-tokyo.ac.jp/~toxicol/index.html
• [Remarks] 東京大学大学院薬学系研究科細胞情報学教室ホームページ
  • URL: http://www.f.u-tokyo.ac.jp/~toxicol/index.html