Characterization of human LNX, a novel ligand of Numb protein X that is downregulated in human gliomas
Characterization of human LNX, a novel ligand of Numb protein X that is downregulated in human gliomas
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DOI：
10.1016/j.biocel.2005.02.028
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发表时间：
2005-11-01
影响因子：
4
通讯作者：
Lu, YC
中科院分区：
文献类型：
--
作者：
Chen, JX;Xu, J;Lu, YC
胶质瘤是中枢神经系统的主要肿瘤，有多种不同的肿瘤类型。Numb蛋白X配体(LNX)是一种含有PDZ结构域的蛋白，与细胞命运决定因子Num相互作用。用基因芯片技术分析了13,939个基因在18个胶质瘤中的表达。Northern印迹结果表明，人LNX在包括低级别和高级别胶质瘤中100%表达下调。原位杂交结果显示，LNX在胶质瘤细胞胞浆中低表达。因此，LNX可能成为脑胶质瘤的诊断标记物和潜在的治疗靶点。利用酵母双杂交技术筛选与人LNX相互作用的重要蛋白。结果表明，人LNX通过PDZ结构域与Ski相互作用蛋白(SKIP)相互作用。免疫共沉淀结果表明，LNX与SKIP在HEK293细胞中相互作用。LNX可影响Numb亚细胞定位，提示LNX可能作为分子锚将Num定位于其与Notch相互作用的亚细胞位置。参与信号转导和与Numb和Skip相互作用的多个蛋白结合域的存在表明LNX在肿瘤发生中起着重要作用。(C)2005年由爱思唯尔有限公司出版。
Gliomas are major tumors of the central nervous system with a wide spectrum of different tumor types. Ligand of Numb protein X (LNX) is PDZ domain containing protein that interacts with cell fate determinant Numb. cDNA microarray analysis was used to determine the expression of 13,939 genes in a set of 18 gliomas. It showed that human LNX was downregulated in 100% of gliomas including low- and high-grade ones, which was confirmed by Northern blot. In situ hybridization analysis revealed that LNX was lowly expressed in cytoplasm of glioma cells. Thus, LNX might act as a diagnostic marker and a potential therapeutic target for glioma. Two-hybrid screen in yeast was used to identify human LNX interacting proteins important for LNX function. It showed that human LNX interacted with Ski interacting protein (SKIP) via PDZ domains. The co-immunoprecipitation results suggested that LNX interacted with SKIP in HEK293 cells. LNX could affect the subcellular localization of Numb, which indicated that LNX might function as a molecular anchor that localized Numb to the subcellular site of its interaction with Notch. The presence of multiple protein binding domains involved in signal transduction and interaction with Numb and SKIP suggested an important role for LNX in tumorogenesis. (c) 2005 Published by Elsevier Ltd.