Analysis of degradation mechanisms through WDR26 in Wnt signaling

• Project/Area Number: 15K08262
• 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): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: WDR26 / Wnt / beta-catenin / ユビキチン化 / シグナル伝達 / アフリカツメガエル / β-catenin / アフリカ爪ガエル

Outline of Final Research Achievements

Wnt signaling pathway plays important roles in disease and embryonic development. Stability of cytoplasmic beta-catenin is a key feature of Wnt signaling pathway.
In this study, I first identified WDR26 as an Axin-binding protein by MS analysis. Then I analyzed the function of WDR26 in the degradation of beta-catenin of Wnt signaling pathway.
As results, I found that WDR 26 promoted beta-catenin ubiquitination through binding with Axin, other GID-related genes also ubiquitinated and reduced beta-catenin protein, novel lysine residues of were ubiquitinated during degradation of beta-catenin.

Research Products

• [Journal Article] Roles of Xenopus chemokine ligand CXCLh (XCXCLh) in early embryogenesis. (2018)
  • Author(s): Goto T., Ito Y., Michiue T.
  • Journal Title: Dev Growth Differ. Volume: 印刷中 Issue: 4 Pages: 226-238
  • DOI: 10.1111/dgd.12432
  • Peer Reviewed
• [Journal Article] High variability of expression profiles of homeologous genes for Wnt, Hh, Notch, and Hippo signaling pathways in Xenopus laevis. (2017)
  • Author(s): Michiue T, Yamamoto T, Yasuoka Y, Goto T, Nakayama T, Nagura K, Ikeda T, Taira M, Kinoshita T
  • Journal Title: Dev. Biol. Volume: 印刷中 Issue: 2 Pages: 270-290
  • DOI: 10.1016/j.ydbio.2016.12.006
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] WDR26 is a new partner of Axin1 in the canonical Wnt signaling pathway (2016)
  • Author(s): Goto T., Matsuzawa J., Iemura S., Natsume T., Shibuya H.
  • Journal Title: FEBS Letters Volume: 印刷中
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Selective inhibition of the kinase DYRK1A by targeting its folding process (2016)
  • Author(s): Kii I., Sumida Y., Goto T., Sonamoto R., Okuno Y., Yoshida S., Kato-Sumida T., Koike Y., Abe M., Nonaka Y., Ikura T., Ito N., Shibuya H., Hosoya T., Hagiwara M.
  • Journal Title: Nat. Commun. Volume: 該当なし Issue: 1 Pages: 11391-11391
  • DOI: 10.1038/ncomms11391
  • NAID: 120005770755
  • Peer Reviewed / Open Access
• [Presentation] beta-catenin の分解におけるWDR26 の機能解析 (2017)
  • Author(s): 後藤利保
  • Organizer: 第１１回ツメガエル研究集会
• [Presentation] WDR26 shows novel ubiquitination sites in beta-catenin degradation. (2016)
  • Author(s): 後藤利保、松澤純平、家村俊一郎、夏目徹、澁谷浩司
  • Organizer: 第３９回日本分子生物学会
  • Place of Presentation: パシフィコ横浜、横浜
• [Presentation] WDR26 is a new patner of Axin1 in canonical Wnt signaling Pathway. (2015)
  • Author(s): 後藤利保、松澤純平、家村俊一郎、夏目徹、澁谷浩司
  • Organizer: 第38回日本分子生物学会年会
  • Place of Presentation: 神戸国際展示場（兵庫県 神戸市）
  • Year and Date: 2015-12-01