Regulation of cancer cell growth by regulation of glucose metabolism by ubiquitin-like protein MNSF

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K06546
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43030:Functional biochemistry-related
• Research Institution: Shimane University
• Principal Investigator: Morihiko Nakamura 島根大学, 学術研究院医学・看護学系, 教授 (20155865)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: ユビキチン / HIF / 糖代謝

Outline of Final Research Achievements

Monoclonal non-specific suppressor factor β (MNSFβ) is a ubiquitously expressed member of the ubiquitin-like family that has been involved in various biological functions. Previous studies have demonstrated that MNSFβ regulates glycolysis and enhances cell proliferation in the macrophage-like cell line RAW264.7. In this study, we showed that MNSFβ regulates HIF-1α-mediated metabolic reprogramming. In RAW264.7 cells, MNSFβ siRNA increased oxygen consumption rate and ROS production, but decreased ATP levels. The rate of ATP reduction upon addition of oligomycin, an inhibitor of mitochondrial ATP synthase, was significantly greater in cells with MNSFβ knockdown. In addition, the expression levels of HIF-1α protein and mRNA were decreased by MNSFβ siRNA. The effect of MNSFβ on glucose metabolism was examined in murine peritoneal macrophages, but there were no changes in lactate production, glucose consumption, or ROS production.

Free Research Field

生物化学

Academic Significance and Societal Importance of the Research Achievements

ユビキチン様タンパク質MNSFβの役割として、世界で初めて糖代謝制御機能について詳細に明らかにした。この研究成果は、本研究領域へ与えるインパクトは極めて大きい。これまでアポトーシス制御など多様な機能について明確にしてきたが、今回の研究成果により、MNSFβは生命の根幹に関与する機能を有すると推察される。