ROLE OF CD133 IN TUMORIGENESIS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 CD 133是一种与小鼠Prominin同源的五跨膜糖蛋白。 它最初被单克隆抗体AC 133鉴定为CD 34+细胞亚群上的干细胞标志物。 CD 133在胶质母细胞瘤、白血病、前列腺癌和结肠癌中过表达。 CD 133引起肿瘤发生的机制尚不清楚。 人Prominin-1的开放阅读框预测为865个氨基酸，分子量为96.8 KD。 然而，抗体识别SDS凝胶上的120 KD单一条带，与蛋白质糖基化一致。 CD 133转录物在多种组织中表达，其中在肾脏、胰腺和胎盘中表达最高。在人视网膜变性（一种常染色体隐性疾病）中已经鉴定了人Prominin-1的位置1878处的单核苷酸缺失，其导致蛋白质的过早截短（Maw，et. 2000）。 CD 133在质膜突起中的定位表明在细胞极性、迁移以及干细胞与邻近细胞和/或细胞外基质的相互作用中起作用。 使用串联亲和纯化（TAP）和质谱，我们希望识别CD 133的结合伴侣，以了解CD 133下游的信号传导事件。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. CD133 is a pentaspan membrane glycoprotein with homology to mouse Prominin. It was initially identified as a stem cell marker on a subset of CD34+ cells by the monoclonal antibody AC133. CD133 is over-expressed in glioblastoma, leukemia, prostate and colon cancers. The mechanism by which CD133 confers tumorigenesis is not understood. The open reading frame of human Prominin-1 predicted a protein of 865 amino acids with a molecular weight of 96.8 KD. The antibody, however, recognizes a 120KD single band on an SDS gel consistent with protein glycosylation. The CD133 transcript is expressed in a variety of tissues, with the highest expression being in kidney, pancreas and placenta. A single nucleotide deletion at position 1878 of human Prominin-1 which results in premature truncation of the protein, has been identified in human retinal degeneration, an autosomal recessive disorder (Maw, et. al. 2000). The localization of CD133 in the protrusions of plasma membrane suggests a role in cell polarity, migration, and interaction of stem cells with neighboring cells and/or extra-cellular matrix. Using Tandem Affinity Purification (TAP) and mass spectroscopy, we hope to identify binding partners of CD133 in order to understand signaling events downstream of CD133.