Department of Medical Genetics, Peking University School of Basic Medical Sciences, Beijing 100191, China; Peking University Center for Human Disease Genomics, Beijing 100191, China.
Peking University Center for Human Disease Genomics, Beijing 100191, China; Department of Immunology, Peking University School of Basic Medical Science, Key Laboratory of Medical Immunology, Beijing 100191, China.
Exp Cell Res. 2019 Mar 1;376(1):1-10. doi: 10.1016/j.yexcr.2019.01.023. Epub 2019 Feb 1.
Glucoside xylosyltransferase2 (GXYLT2), a member of the human α-1,3-D-xylosyltransferases, functions to modify the first xylose to the O-Glucose residue on epidermal growth factor (EGF) repeats of Notch receptors. It is well-established that the Notch signaling pathway plays a critical role in proper development and homeostasis. However, the regulatory role of EGF xylosylation in Notch signaling and different cell activities in human cells remains unknown. In this study, we showed that knockdown of GXYLT2 suppressed human cell proliferation and induced G1/S phase cell cycle arrest. GXYLT2 downregulation also inhibited cell migration and invasion, whereas the overexpression of GXYLT2 had the opposite effects. Additionally, GXYLT2 activated Notch signaling and promoted the phosphorylation of MAPKs but not PI3K and Akt. Taken together, our findings indicated that GXYLT2 plays an important role in cell activities via regulation of the Notch signaling.
木糖基转移酶 2（GXYLT2）是人类α-1,3-D-木糖基转移酶家族的成员，其功能是将第一个木糖修饰到 Notch 受体表皮生长因子（EGF）重复序列的 O-葡萄糖残基上。 Notch 信号通路在正常发育和内稳态中起着关键作用，这一点已得到充分证实。然而，EGF 木糖基化在 Notch 信号传导以及人类细胞中的不同细胞活性中的调节作用尚不清楚。在本研究中，我们表明 GXYLT2 的敲低抑制了人细胞的增殖并诱导了 G1/S 期细胞周期停滞。GXYLT2 的下调还抑制了细胞迁移和侵袭，而 GXYLT2 的过表达则具有相反的效果。此外，GXYLT2 激活了 Notch 信号通路，并促进了 MAPKs 的磷酸化，但不促进 PI3K 和 Akt 的磷酸化。总之，我们的研究结果表明，GXYLT2 通过调节 Notch 信号通路在细胞活动中发挥重要作用。
