TNF-α-induced Inhibition of Protein Myristoylation Via Binding Between NMT1 and Sorbs2 in Osteoblasts

Background/Aim: Bone resolution due to tumor invasion often occurs on the surface of the jaw and is important for clinical prognosis. Although cytokines, such as TNF-α are known to impair osteoblasts, the underlying mechanism remains unclear. Protein myristoylation, a post-translational modification, plays an important role in the development of immune responses and cancerization of cells. A clear understanding of the mechanisms underlying this involvement will provide insights into molecular-targeted therapies. N-myristoyltransferase1 (NMT1), a specific enzyme involved in myristoylation, is expressed in cancer cells and in other normal cells, suggesting that changes in myristoylation may result from the regulation of NMT1 in cancer cells. Materials and Methods: Using newly emerging state-of-the-art techniques such as the Click-it assay, RNA interference, mass spectrometry, immunoprecipitation, immunocytochemistry, and western blotting, the expression of myristoylated proteins and the role of TNF-α stimulation on NMT1 and Sorbs2 binding were evaluated in a murine osteoblastic cell line (MC3T3-E1). Results: The expression of myristoylated proteins was detected; however, TNF-α stimulation resulted in their inhibition in MC3T3-E1 cells. The expression of NMT1 also increased. Immunoprecipitation and mass spectrometry identified Sorbs2 as a novel binding protein of NMT1, which upon TNF-α stimulation, inhibited myristoylation. Conclusion: The binding between NMT1 and Sorbs2 can regulate.