Analysis of beta-catenin nuclear translocation mechanism through IQGAP1 in Wnt signaling.

• Project/Area Number: 24590344
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: GOTO Toshiyasu 東京医科歯科大学, 難治疾患研究所, 准教授 (00517518)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: IQGAP1 / Wnt / シグナル伝達 / β-catenin / 核内移行 / アフリカツメガエル

Outline of Final Research Achievements

Wnt signaling pathway plays an important role in cancer and embryonic development, a key feature of Wnt signaling activation is beta-catenin nuclear translocation.
In this study, we first identified IQGAP1 as a scaffold protein that binds DVL, one of Wnt signaling molecules. Then we analyzed the function of IQGAP1 in Wnt signaling pathway.
As a result, (1) IQGAP1 functioned as a positive regulator of Wnt signaling. (2) IQGAP1 complexed with beta-catenin and DVL2. (3) IQGAP1 was capable to bind with Importin-beta5 and Ran so that the above complex translocated into the nucleus.

Research Products

• [Journal Article] IQGAP1 functions as a modulator of Dishevelled nuclear localization in Wnt signaling (2013)
  • Author(s): Goto, T., Sato, A., Shimizu, M., Adachi, S., Satoh, K., Iemura, S., Natsume, T. and Shibuya, H
  • Journal Title: PLoS One Volume: 8 Issue: 4 Pages: e60865-e60865
  • DOI: 10.1371/journal.pone.0060865
  • Peer Reviewed
• [Journal Article] IQGAP1 regulates nuclear localization of β-Catenin via importin-β5 in Wnt signaling. (2013)
  • Author(s): Goto. T, Sato, A., Adachi, S., Iemura, S., Natsume, T. and Shibuya, H.
  • Journal Title: J. Biol. Chem. Volume: 288 Issue: 51 Pages: 36351-36360
  • DOI: 10.1074/jbc.m113.520528
  • Peer Reviewed
• [Journal Article] WNK4 is an essential effector of anterior formation in FGF signaling (2013)
  • Author(s): Shimizu, M., Goto, T., Sato, A. and Shibuya, H
  • Journal Title: Genes Cells Volume: 18 Issue: 6 Pages: 442-449
  • DOI: 10.1111/gtc.12048
  • Peer Reviewed
• [Journal Article] Characterization of CXC-type chemokine molecules in early Xenopus laevis development. (2013)
  • Author(s): Goto T, et al.
  • Journal Title: Int J Dev Biol. Volume: 57 Issue: 1 Pages: 41-47
  • DOI: 10.1387/ijdb.120223ma
  • Peer Reviewed
• [Presentation] IQGAP1によるß-cateninの核内移行の調節機構の解析 (2013)
  • Author(s): ○後藤利保、佐藤淳、足立俊吾、家村俊一郎、夏目徹、澁谷浩司
  • Organizer: 日本分子生物学会
  • Place of Presentation: 神戸