Redox signaling and cancer formation

• Project/Area Number: 20013025
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Osaka University
• Principal Investigator: MIKI Hiroaki Osaka University, 蛋白質研究所, 教授 (80302602)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥18,000,000 (Direct Cost: ¥18,000,000); Fiscal Year 2009: ¥9,000,000 (Direct Cost: ¥9,000,000); Fiscal Year 2008: ¥9,000,000 (Direct Cost: ¥9,000,000)
• Keywords: Wnt / Dishevelled (Dvl) / nucleoredoxin (NRX) / がん / Nucleoredoxin (NRX) / Dishevelled(Dvl) / Nucleoredoxin(NRX)

Research Abstract

I investigated the function of NRX that binds to Dvl, a Wnt signal transducer. Mice deficient for NRX gene were perinatally lethal and showed abnormal development of their bones and heart. Wnt signaling was hyperactivated in cells obtained form calvaria, but was downregulated in cells from the heart. This unexpected decrease in the activity of Wnt signaling was due to the reduction of Dvl proteins caused by augmented ubiquitination. Also, I discovered that Fli-I is a novel binding partner for NRX, and found that NRX inhibits the innate immune response by linking Fli-I to MyD88.

Research Products

• [Journal Article] Nucleoredoxin negatively regulates Toll-like receptor 4 signaling via recruitment of Flightless-I to Myeloid differentiation primary response gene (88). (2010)
  • Author(s): Hayashi T, Funato Y, Terabayashi T, Morinaka A, Sakamoto R, Ichise H, Fukuda H, Yoshida N, Miki H
  • Journal Title: J. Biol. Chem. (in press)
  • Peer Reviewed
• [Journal Article] Kif26b, a kinesin family gene, regulates adhesion of the embryonic kidney mesenchyme. (2010)
  • Author(s): Uchiyama Y, Sakaguchi M, Terabayashi T, Inenaga T, Inoue S, Kobayashi C, Oshima N, Kiyonari H, Nakagata N, Sato Y, Sekiguchi K, Miki H, Araki E, Fujimura S, Tanaka S, Nishinakamura R
  • Journal Title: Proc. Natl. Acad. Sci. USA (in press)
  • Peer Reviewed
• [Journal Article] Par1b/MARK2 phosphorylates kinesin-like motor protein GAKIN/KIF13B to regulate axon formation. (2010)
  • Author(s): Yoshimura Y, Terabayashi T, Miki H
  • Journal Title: Mol. Cell. Biol. 30 Pages: 2206-2219
  • Peer Reviewed
• [Journal Article] Redox regulation of Wnt signalling via nucleoredoxin. (2010)
  • Author(s): Funato Y, Miki H
  • Journal Title: Free Radic. Res. 44 Pages: 379-388
  • Peer Reviewed
• [Journal Article] Discovery of candidate disease genes in ENU-induced mouse mutants by large-scale sequencing identifies a splice-site mutation in nucleoredoxin. (2009)
  • Author(s): Boles MK, Wilkinson BM, Wilming L, Liu B, Probst FJ, Harrow J, Grafham D, Hentges KE, Woodward LP, Maxwell A, Mitchell K, Risley MD, Johnson R, Hirschi K, Lupski JR, Funato Y, Miki H, Marcin-Garcia P, Mattews L, Coffey AJ, Parker A, Hubbard TJ, Rogers J, Bradley A, Adams DJ, Justice MJ.
  • Journal Title: PLoS Genet. 5
  • Peer Reviewed
• [Journal Article] A coated vesicle-associated kinase of 104 kDa (CVAK104) induces lysosomal degradation of frizzled 5 (Fzd5). (2009)
  • Author(s): Terabayashi T, Funato Y, Fukuda M, Miki H
  • Journal Title: J. Biol. Chem. 284 Pages: 26716-26724
  • Peer Reviewed
• [Journal Article] Sufu recruits GSK3beta for efficient processing of Gli3. (2009)
  • Author(s): Kise Y, Morinaka A, Teglund S, Miki H
  • Journal Title: Biochem. Biophys. Res. Commun. 387 Pages: 569-574
  • Peer Reviewed
• [Journal Article] Discovery of candidate disease genes in ENU-induced mouse mutants by large-scale sequencing identifies a splice-site mutation in nucleoredoxin. (2009)
  • Author(s): Boles, et al.
  • Journal Title: PLoS Genetics VOL.5
  • Peer Reviewed
• [Journal Article] A coated vesicle-associated kinase of 104 kDa (CVAK104) induces lysosomal degradation of frizzled 5 (Fzd5). (2009)
  • Author(s): Terabayashi, et al.
  • Journal Title: Journal of Biological Chemistry VOL.284 Pages: 26716-26714
  • Peer Reviewed
• [Journal Article] Sufu recruits GSK3beta for efficient processing of Gli3. (2009)
  • Author(s): Kise, et al.
  • Journal Title: Biochemical and Biophysical Research Communications VOL.387 Pages: 569-574
  • Peer Reviewed
• [Journal Article] Dishevelled-induced phosphorylation regulates membrane localization of Par1b. (2008)
  • Author(s): Terabayashi T, Funato Y, Miki H
  • Journal Title: Biochem. Biophys. Res. Commun. 375 Pages: 660-5
  • Peer Reviewed
• [Journal Article] Nucleoredoxin regulates the Wnt/planar cell polarity pathway in Xenopus. (2008)
  • Author(s): Funato Y, Michiue T, Terabayashi T, Yukita A, Danno H, Asashima M, Miki H
  • Journal Title: Genes Cells. 13 Pages: 965-75
  • Peer Reviewed
• [Journal Article] Dishevelled-induced phosphorylation regulates membrane localization of Parlb (2008)
  • Author(s): Takeshi Terabayashi, et.al.
  • Journal Title: Biochem. Biophys. Res. Commun 375 Pages: 660-665
  • Peer Reviewed
• [Journal Article] Nucleoredoxin regulates the Wnt/planar cell polarity pathway in Xenopus (2008)
  • Author(s): Yosuke Funato, et.al.
  • Journal Title: Genes. Cells 13 Pages: 965-975
  • Peer Reviewed
• [Presentation] タンパク質の酸化修飾によるシグナル伝達の制御 (2009)
  • Author(s): 三木裕明、船戸洋祐、森中紹文
  • Organizer: 第82回日本生化学会大会シンポジウム
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-23
• [Presentation] タンパク質の酸化修飾によるシグナル伝達の制御 (2009)
  • Author(s): 三木裕明、船戸洋祐、森中紹文
  • Organizer: 日本生化学会
  • Place of Presentation: 神戸国際会議場(兵庫県)
  • Year and Date: 2009-10-23
• [Presentation] セマフォリン3AシグナルにおけるCRMP2の酸化依存的リン酸化と成長円錐崩壊 (2009)
  • Author(s): 森中紹文、船戸洋祐、三木裕明
  • Organizer: 第61回日本細胞生物学会大会ミニシンポジウム
  • Place of Presentation: 名古屋
  • Year and Date: 2009-06-02
• [Presentation] レドックス応答性因子nucleoredoxinによるWntシグナルの制御 (2008)
  • Author(s): 三木裕明
  • Organizer: 第61回日本酸化ストレス学会学術集会シンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2008-06-19
• [Presentation] レドックス応答性因子nucleoredoxinによるWntシグナルの制御 (2008)
  • Author(s): 三木裕明
  • Organizer: 日本酸化ストレス学会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2008-06-19
• [Remarks]
  • URL: http://www.protein.osaka-u.ac.jp/intra_signal/index.html
• [Remarks]
  • URL: http://www.protein.osaka-u.ac.jp/intra_signal/index.html