Nakamura Morihiko, Yamasaki Kyoko, Kono Megumi
The Department of Cooperative Medical Research, Office for Regional Collaboration and Innovation, Shimane University, Izumo, 693-8501, Japan.
Biochem Biophys Rep. 2022 Dec 21;33:101414. doi: 10.1016/j.bbrep.2022.101414. eCollection 2023 Mar.
Monoclonal non-specific suppressor factor β (MNSFβ) is a universally expressed ubiquitin-like protein that has multiple biological functions. MNSFβ modifies its target molecules through covalent conjugation. Most recently, we identified a molecular chaperone, HSC70, that facilitates the stabilization of aggregable MNSFβ. In the current study, we determined the role of HSC70 in stabilizing unstable MNSFβ. HSC70 promoted the correct folding of MNSFβ both and . We also examined the regulatory function of MNSFβ in cell proliferation and glycolysis. MNSFβ siRNA and HSC70 siRNA treatment attenuated lactate release from Raw264.7 macrophage-like cells. MNSFβ siRNA inhibited glucose uptake in Raw264.7 cells. We found that glucose transporter 1 (GLUT1) is an important membrane protein involved in the regulatory function of MNSFβ during glycolysis. MNSFβ siRNA inhibited the increased GLUT1 expression in LPS-stimulated cells, suggesting that MNSFβ controls the inflammatory response through GLUT1 regulation. We identified several important molecules, including lactate dehydrogenase A, which are regulated by MNSFβ and involved in glucose metabolism. Here we firstly report that MNSFβ regulates glycolysis and promotes cell proliferation.
单克隆非特异性抑制因子β（MNSFβ）是一种普遍表达的类泛素蛋白，具有多种生物学功能。MNSFβ通过共价结合修饰其靶分子。最近，我们鉴定出一种分子伴侣HSC70，它有助于可聚集的MNSFβ的稳定。在本研究中，我们确定了HSC70在稳定不稳定的MNSFβ中的作用。HSC70在体外和体内均促进了MNSFβ的正确折叠。我们还研究了MNSFβ在细胞增殖和糖酵解中的调节功能。MNSFβ siRNA和HSC70 siRNA处理减弱了Raw264.7巨噬细胞样细胞中乳酸的释放。MNSFβ siRNA抑制了Raw264.7细胞中的葡萄糖摄取。我们发现葡萄糖转运蛋白1（GLUT1）是一种重要的膜蛋白，参与MNSFβ在糖酵解过程中的调节功能。MNSFβ siRNA抑制了LPS刺激细胞中GLUT1表达的增加，表明MNSFβ通过GLUT1调节来控制炎症反应。我们鉴定出了几种重要的分子，包括乳酸脱氢酶A，它们受MNSFβ调节并参与葡萄糖代谢。在此我们首次报道MNSFβ调节糖酵解并促进细胞增殖。
