Inhibitory mechanism of cell proliferation by a novel X-linked tumor suppressor Nrk

2013 Fiscal Year Final Research Report

• Project/Area Number: 24650610
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Carcinogenesis
• Research Institution: Tokyo Institute of Technology
• Principal Investigator: KOMADA Masayuki 東京工業大学, 生命理工学研究科, 准教授 (10225568)
• Co-Investigator(Kenkyū-buntansha): DENDA Kimitoshi 東京工業大学, 大学院生命理工学研究科, 助教 (50212064)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 癌 / 細胞・組織 / シグナル伝達 / 蛋白質 / 酵素

Research Abstract

1) We identified CSIG (cellular senescence-inhibited gene), a protein which inhibits PTEN in the Akt signal transduction pathway, as a Nrk-binding protein in placenta, suggesting that Nrk inhibits the proliferation of spongiotrophoblasts in placenta by inhibiting the Akt signaling pathway. We also found that the level of a cell cycle inhibitor protein p27 is downregulated in Nrk knockout spongiotrophoblasts, suggesting that Nrk increases p27 gene expression or inhibits p27 protein degradation in spongiotrophoblasts.
2) We found that the estrogen level is elevated in the blood and ovary of mammary tumor-harboring Nrk knockout female mice, suggesting that the high estrogen level in the blood causes mammary tumors in Nrk knockout mice. In addition, we found that Nrk is expressed in lactating and old (~12 months) wild-type mice, suggesting that Nrk suppresses the overgrowth of mammary epithelial cells by downregulating estrogen synthesis in the ovary.

Research Products

• [Journal Article] Ubiquitin-interacting motifs confer full catalytic activity, but not ubiquitin chain substrate specificity, to deubiquitinating enzyme USP37 (2014)
  • Author(s): Tanno, H., Shigematsu, T., Nishikawa, S., Hayakawa, A., Denda, K., Tanaka, T., and Komada, M.
  • Journal Title: J. Biol. Chem. Volume: 289 Pages: 2415-2423
  • Peer Reviewed
• [Journal Article] In vivo assembly of the axon initial segment in motor neurons (2013)
  • Author(s): Le Bras, B., Fréal, A., Czarnecki, A., Legendre, P., Bullier, E., Komada, M., Brophy, P.J., Davenne, M., and Couraud, F.
  • Journal Title: Brain Struct. Funct.
  • DOI: 10.1007/s00429-013-0578-7
  • Peer Reviewed
• [Journal Article] Involvement of Src in the membrane skeletal complex, MPP6-4.1G, in Schmidt-Lanterman incisures of mouse myelinated nerve fibers in PNS (2013)
  • Author(s): Terada, N., Saitoh, Y., Ohno, N., Komada, M., Yamauchi, J., and Ohno S.
  • Journal Title: Histochem. Cell Biol. Volume: 140 Pages: 213-222
  • Peer Reviewed
• [Journal Article] Essential function of protein 4.1G in targeting of MPP6 into Schmidt-Lanterman incisures in myelinated nerves (2012)
  • Author(s): Terada, N., Saitoh, Y., Ohno, N., Komada, M., Saitoh, S., Peles, E., and Ohno, S.
  • Journal Title: Mol. Cell. Biol. Volume: 32 Pages: 199-205
  • Peer Reviewed
• [Presentation] Negative regulation of mammary epithelial cell proliferation by protein kinase Nrk (2013)
  • Author(s): 柳川享世、稲谷卓也、伝田公紀、駒田雅之
  • Organizer: 第36回日本分子生物学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2013-12-05
• [Presentation] 分娩発来をもたらす胎盤特異的なプロテインキナーゼNrkが与るシグナル伝達 (2013)
  • Author(s): 伝田公紀、井田加奈子、廣崎賢、岡本直樹、柳川享世、林宣宏、駒田雅之
  • Organizer: 第36回日本分子生物学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2013-12-04
• [Remarks]
  • URL: http://www.komada-lab.bio.titech.ac.jp