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[O3-E-AM2-01] Alteration of O-GlcNAc transferase localization induced by PP2A inhibition in osteoblast
Keywords:骨芽細胞、蛋白質脱リン酸化、蛋白質糖鎖化
Protein post-translational modifications are important in various cell dynamics including osteoblastic differentiation. O-GlcNAc glycosylation does not occur when the target proteins' serine/threonine residue is phosphorylated. Therefore, O-GlcNAc glycosylation and protein dephosphorylation are considered to be related. We reported that decreased expression and activity of the protein phosphatase PP2A are important for osteoblast differentiation. This study analyzed the effects of PP2A activity and localization of O-GlcNAc transferase OGT during osteoblast differentiation. Treatment of osteoblasts MC3T3-E1 with okadaic acid (OA), a PP2A inhibitor, translocated OGT from the nucleus to the nucleus. When MC3T3-E1 cells were cultured in a differentiation-inducing medium, OGT translocated from the nucleus to the cytoplasm from day 1 to 3. High concentrations of glucose increased PP2A activity and inhibited OGT translocation. In addition, O-GlcNAc glycosylation of the transcription factors Runx2 and Sp7, which are important for osteoblastic differentiation, was enhanced in the presence of high glucose. These results suggest that nuclear OGT is responsible for O-GlcNAc-type glycosylation of Runx2 and Sp7 in osteoblasts. It is suggested that decreased activity of PP2A induces nuclear export of OGT, reduces glycosylation of these transcription factors, and promotes osteoblast differentiation. A high concentration of glucose maintains PP2A activity at a high level, which is thought to inhibit OGT nuclear export and suppress osteoblast differentiation.