Characterization of PRL as a redox-sensing molecule

• Project/Area Number: 22770195
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Cell biology
• Research Institution: Osaka University
• Principal Investigator: FUNATO Yosuke 大阪大学, 微生物病研究所, 助教 (60505775)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 細胞内情報伝達 / PRL / マグネシウム / がん転移 / MEP50 / PSMC6

Research Abstract

I searched for a novel interacting protein of PRL, a protein tyrosine phosphatase involved in tumor metastasis, and identified MagEx as a major binding partner of PRL. MagEx interacts with PRL in a redox-dependent manner. Functional analyses revealed that MagEx stimulates Mg^<2+>-efflux. Overexpression of PRL inhibits the MagEx-dependent Mg^<2+>-efflux, which is restored by stimulating the cells with hydrogen peroxide. Mg^<2+>-efflux by MagEx results in suppression of Akt/ mTOR signaling, which is cancelled by co-expression of PRL. Furthermore, experimental metastasis analyses in mice reveal that RNAi-mediated knockdown of MagEx resulted in increased metastatic nodules in lungs. Collectively, these results indicate that MagEx is the molecular target for PRL.

Research Products

• [Journal Article] Regulation of intracellular signalling through cysteine oxidation by reactive oxygen species (2012)
  • Author(s): Miki, H., and Funato, Y
  • Journal Title: J. Biochem Volume: 151 Pages: 255-261
  • NAID: 10031166064
  • Peer Reviewed
• [Journal Article] Regulation of intracellular signalling through cysteine oxidation by reactive oxygen species (2012)
  • Author(s): Miki, H.
  • Journal Title: Journal of Biochemistry Volume: 151 Issue: 3 Pages: 255-261
  • DOI: 10.1093/jb/mvs006
  • Peer Reviewed
• [Journal Article] Oligomeric peroxiredoxin-I is an essential intermediate for p53 to activate MST1 kinase and apoptosis (2011)
  • Author(s): Morinaka, A., Funato, Y., Uesugi, K., and Miki, H
  • Journal Title: Oncogene Volume: 30 Pages: 4208-4218
  • Peer Reviewed
• [Journal Article] Thioredoxin mediates oxidation-dependent phosphorylation of CRMP2 and growth cone collapse (2011)
  • Author(s): Morinaka, A., Yamada, M., Itofusa, R., Funato, Y., Yoshimura, Y., Nakamura, F., Yoshimura, T., Kaibuchi, K., Goshima, Y., Hoshino, M., Kamiguchi, H., and Miki, H.
  • Journal Title: Science Signal Volume: 4
  • Peer Reviewed
• [Journal Article] An interaction between human Sec63 and nucleoredoxin may provide the missing link between the SEC63 gene and polycystic liver disease (2011)
  • Author(s): Muller, L., Funato, Y., Miki, H., and Zimmermann, R.
  • Journal Title: FEBS Lett Volume: 585 Pages: 596-600
  • Peer Reviewed
• [Journal Article] Thioredoxin mediates oxidation-dependent phosphorylation of CRMP2 and growth cone collapse (2011)
  • Author(s): Morinaka A, Yamada M, Itofusa R, Funato Y, Yoshimura Y, Nakamura F, Yoshimura T, Kaibuchi K, Goshima Y, Hoshino M, Kamiguchi H, Miki H
  • Journal Title: Science Signaling Volume: 4(179) Issue: 170
  • DOI: 10.1126/scisignal.2001127
  • Peer Reviewed
• [Journal Article] Oligomeric peroxiredoxin I is an essential intermediate for p53 to activate MST1 kinase and apoptosis (2011)
  • Author(s): Morinaka, A.
  • Journal Title: Oncogene Volume: 30 Issue: 40 Pages: 4208-4218
  • DOI: 10.1038/onc.2011.139
  • Peer Reviewed
• [Journal Article] An interaction between human Sec63 and nucleoredoxin may provide the missing link between the SEC63 gene and polycystic liver disease. (2011)
  • Author(s): Muller, L., Funato, Y.
  • Journal Title: FEBS letters Volume: 585 Pages: 595-600
  • Peer Reviewed
• [Journal Article] Oligomeric peroxiredoxin I is an essential intermediate for p53 to activate MST1 kinase and apoptosis. (2011)
  • Author(s): Morinaka, A., Funato, Y.
  • Journal Title: Oncogene Volume: (掲載確定)
  • Peer Reviewed
• [Journal Article] Nucleoredoxin sustains Wnt/β-catenin signaling by retaining a pool of inactive Dishevelled protein (2010)
  • Author(s): Funato, Y., Terabayashi, T., Sakamoto, R., Okuzaki, D., Ichise, H., Nojima, H., Yoshida, N., and Miki H.
  • Journal Title: Curr. Biol Volume: 20 Pages: 1945-1952
  • Peer Reviewed
• [Journal Article] Nucleoredoxin negatively regulates Toll-like receptor 4 signaling via recruitment of flightless-I to myeloid differentiation primary response gene (2010)
  • Author(s): #Hayashi, T., # Funato, Y., Terabayashi, T., Morinaka, A., Sakamoto, R., Ichise, H., Fukuda, H., Yoshida, N., and Miki, H.
  • Journal Title: J. Biol. Chem Volume: 285 Pages: 18586-18593
  • Peer Reviewed
• [Journal Article] Redox regulation of Wnt signalling via nucleoredoxin (2010)
  • Author(s): Funato, Y. and Miki, H.
  • Journal Title: Free Radic. Res Volume: 44 Pages: 379-388
  • Peer Reviewed
• [Journal Article] Redox regulation of Wnt signalling via nucleoredoxin (2010)
  • Author(s): Funato, Y.
  • Journal Title: Free Radical Research Volume: 44 Pages: 379-388
  • Peer Reviewed
• [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.
  • Journal Title: Journal of Biological Chemistry Volume: 285 Pages: 18586-18593
  • Peer Reviewed
• [Journal Article] Nucleoredoxin sustains Wnt/β-catenin signaling by retaining a pool of inactive dishevelled protein (2010)
  • Author(s): Funato, Y.
  • Journal Title: Current Biology Volume: 20 Pages: 1945-1952
  • Peer Reviewed
• [Presentation] Nucleoredoxin sustains Wnt/β-catenin signaling by keeping inactive pool of Dishevelled (2010)
  • Author(s): 船戸洋佑、三木裕明
  • Organizer: 第26回熊本医学・生物科学シンポジウム
  • Place of Presentation: 熊本
  • Year and Date: 2010-06-19
• [Presentation] Nucleoredoxin regulates the intensity of the Wnt/β-catenin pathway through stabilization of Dishevelled (2010)
  • Author(s): 船戸洋佑
  • Organizer: 第62回日本細胞生物学会大会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2010-05-20
• [Presentation] NucleoredoxinはDishevelled蛋白質の安定性を制御することによってWnt/ b-catenin経路の活性を調節している (2010)
  • Author(s): 船戸洋佑、寺林健、吉田進昭、三木裕明
  • Organizer: 第62回日本細胞生物学会大会
  • Place of Presentation: 大阪
  • Year and Date: 2010-05-19