Ubiquitin-like protein MNSF is disaggregated and regulates cell proliferation

• Project/Area Number: 17K07335
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Shimane University
• Principal Investigator: Nakamura Morihiko 島根大学, 学術研究院医学・看護学系, 教授 (20155865)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ユビキチン様タンパク質 / 核小体ストレス / ユビキチン類似タンパク質 / 細胞増殖制御 / 核小体ストレス応答 / 分子シャペロン / 脱凝集化

Outline of Final Research Achievements

We found molecular chaperone HSPA8 as a novel partner for ubiquitin-like protein MNSFβ. HSPA8 might promote the folding of the highly aggregable MNSFβ. Indeed, knockdown of HSPA8 significantly reduced the expression of MNSFβ in macrophage cell line Raw264.7 cells. We next examined the effect of HSPA8 on MNSFβ disaggregation. Although MNSFβ formed insoluble aggregation in vitro, HSPA8 significantly inhibited the aggregation of MNSFβ. Because HSPA8 has been reported to migrate from cytoplasm to nucleus during stress, we investigated the intracellular localization of MNSFβ. MNSFβ-GFP fusion protein localizes in the nucleus in unstimulated Hela cells, yet located to the cytoplasm by actinomycin D, a transcription inhibitor. MNSFβ siRNA increased the level of p53 expression in Raw264.7 cells under nutrient starvation conditions. Collectively, MNSFβ regulates cell proliferation through nucleolus stress response.

Academic Significance and Societal Importance of the Research Achievements

今回の実験結果は、ユビキチン様タンパク質ファミリーの研究分野において多大な影響を与える。

Research Products

• [Journal Article] Heat shock protein 60 negatively regulates the biological functions of ubiquitin-like protein MNSFβ in macrophages. (2019)
  • Author(s): Nakamura M, Notsu K, Nakagawa M
  • Journal Title: Molecular and cellular biochemistry Volume: 455 Issue: 1-2 Pages: 29-39
  • DOI: 10.1007/s11010-018-3487-5
  • Peer Reviewed / Open Access
• [Journal Article] Subchronic intravenous toxicity study of biofunctional ZnO and its application as a fluorescence probe for cell-specific targeting. (2019)
  • Author(s): Nakamura M, Watanabe N
  • Journal Title: J Biochem Mol Toxicol. Volume: 33 Issue: 4
  • DOI: 10.1002/jbt.22276
  • Peer Reviewed / Open Access
• [Presentation] ユビキチン様タンパク質MNSFβによる糖代謝制御機序の解明 (2020)
  • Author(s): 高野恵、中村守彦
  • Organizer: 第93回 日本生化学会
• [Presentation] ユビキチン様タンパク質MNSFβによる糖代謝制御機構の解明 (2019)
  • Author(s): 高野恵、野津香織、中村守彦
  • Organizer: 第92回日本生化学会
• [Presentation] Ubiquitin-like protein MNSFβis disaggregated and regulates cell proliferation. (2018)
  • Author(s): Nakamura M., Notsu K.
  • Organizer: 24st International Congress of Biochemistry
  • Int'l Joint Research / Invited
• [Presentation] ユビキチン様タンパク質MNSFβの脱凝集化と細胞増殖制御機構の解明 (2018)
  • Author(s): 野津香織、中村守彦
  • Organizer: 第91回日本生化学会
• [Presentation] ユビキチン様タンパク質MNSFβによる抗炎症作用の機序解明 (2018)
  • Author(s): 高野恵、福間裕紀、野津香織、中村守彦
  • Organizer: 第91回日本生化学会
• [Presentation] Ubiquitin-like protein MNSFβ is deaggregated and regulates cell proliferation (2017)
  • Author(s): Notsu K, Yamasaki K and Nakamura M
  • Organizer: 第90回 日本生化学会
• [Patent(Industrial Property Rights)] 調理支援システム (2017)
  • Inventor(s): 中村守彦
  • Industrial Property Rights Holder: 島根大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2017
  • Acquisition Date: 2020