Ubiquitin-like protein MNSFβ regulates glycolysis and promotes cell proliferation with HSC70 assistance

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 in vitro and in vivo. 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.