Frankel Bruce M, Cachia David, Patel Sunil J, Das Arabinda
Department of Neurosurgery (Divisions of Neuro-Oncology), MUSC Brain & Spine Tumor Program CSB 310, Medical University of South Carolina, Charleston, SC, 29425, USA.
J Mol Neurosci. 2021 Aug;71(8):1714-1722. doi: 10.1007/s12031-021-01808-8. Epub 2021 Feb 17.
The P gene maps precisely to human chromosome sub-band 22q12.1-12.3, a region where loss of heterozygosity has been reported in 30% of astrocytic tumors and associated with progression to anaplasia. Moreover, a putative tumor suppressor gene has been indicated on 22q11 region involved in pathogenesis of ependymal tumors. Our objectives to examine the expression level of novel membrane-associated protein (termed P) encoded by a novel human gene on chromosome 22q12.1-12.3 in glioblastomas and ependymomas. Serial analysis of gene expression (SAGE) and immunofluorescence analysis of the P in the brain tumor tissues were performed. Our analysis revealed that there was high expression of the P mRNA in brain ependymoma and brain well-differentiated astrocytoma libraries. The P protein. P protein contains a high mobility group (HMG) domain at amino acid positions 301 to 360 expressed highly in glioblastoma and ependymoma specimens. Anti-P carboxyl-terminal peptide antibody localized the P protein to the cytoplasmic membranes of protoplasmic astrocytes in the glioblastoma and ependymoma specimens. These results are in good agreement with the SAGE analysis and the predicted transmembrane topology for the P protein and support a possible transmembrane model in which the P contains a predicted transmembrane region with its amino terminus localized to the inside of the cytoplasmic membrane.
P基因精确定位于人类染色体亚带22q12.1 - 12.3,在30%的星形细胞瘤中该区域有杂合性缺失的报道,且与肿瘤进展为间变相关。此外,在与室管膜瘤发病机制相关的22q11区域已发现一个假定的肿瘤抑制基因。我们的目标是检测位于染色体22q12.1 - 12.3上的一个新的人类基因所编码的新型膜相关蛋白(称为P)在胶质母细胞瘤和室管膜瘤中的表达水平。我们对脑肿瘤组织进行了基因表达序列分析(SAGE)和P蛋白的免疫荧光分析。我们的分析显示,在脑室管膜瘤和脑高分化星形细胞瘤文库中P mRNA有高表达。P蛋白。P蛋白在氨基酸位置301至360处含有一个高迁移率族(HMG)结构域,在胶质母细胞瘤和室管膜瘤标本中高表达。抗P羧基末端肽抗体将P蛋白定位于胶质母细胞瘤和室管膜瘤标本中原浆性星形胶质细胞的细胞质膜上。这些结果与SAGE分析以及P蛋白预测的跨膜拓扑结构高度一致,支持了一种可能的跨膜模型,即P蛋白含有一个预测的跨膜区域,其氨基末端定位于细胞质膜内侧。