Department of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829, Japan.
Department of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829, Japan.
Biochem Biophys Res Commun. 2014 Jul 18;450(1):588-92. doi: 10.1016/j.bbrc.2014.06.013. Epub 2014 Jun 10.
Although the Ewing sarcoma (EWS) proto-oncoprotein is found in the nucleus and cytosol and is associated with the cell membrane, the regulatory mechanisms of its subcellular localization are still unclear. Here we found that adipogenic stimuli induce the nuclear localization of EWS in 3T3-L1 cells. Tyrosine phosphorylation in the C-terminal PY-nuclear localization signal of EWS was negative throughout adipogenesis. Instead, an adipogenesis-dependent increase in O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation of EWS was observed. Pharmacological inactivation of O-GlcNAcase in preadipocytes promoted perinuclear localization of EWS. Our findings suggest that the nuclear localization of EWS is partly regulated by the glycosylation.
虽然尤文肉瘤(EWS)原癌蛋白存在于细胞核和细胞质中,并与细胞膜相关,但它的亚细胞定位的调节机制仍不清楚。在这里,我们发现脂肪生成刺激物诱导 3T3-L1 细胞中 EWS 的核定位。在整个脂肪生成过程中,EWS 的 C 末端 PY-核定位信号中的酪氨酸磷酸化呈阴性。相反,观察到 EWS 的 O-连接β-N-乙酰氨基葡萄糖(O-GlcNAc)糖基化在脂肪生成过程中依赖性增加。在脂肪前体细胞中,O-GlcNAcase 的药理学失活促进了 EWS 的核周定位。我们的研究结果表明,EWS 的核定位部分受糖基化调节。