Ubiquitin-like protein MNSF is disaggregated and regulates cell proliferation

2020 Fiscal Year Final Research Report

• 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
• Keywords: ユビキチン様タンパク質 / 核小体ストレス

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.

Free Research Field

生化学

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。