ROLE OF CD133 IN TUMORIGENESIS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 CD133是一种五聚糖膜糖蛋白，与小鼠Prominin同源。它最初被单抗AC133鉴定为CD34+细胞亚群上的干细胞标记物。CD133在胶质母细胞瘤、白血病、前列腺癌和结肠癌中高表达。CD133促进肿瘤发生的机制尚不清楚。人Prominin-1的开放阅读框预测了一个865个氨基酸的蛋白质，其相对分子质量为96.8kD。然而，该抗体识别与蛋白质糖基化一致的十二烷基硫酸钠凝胶上的一条120KD的单一条带。CD133转录本在多种组织中表达，其中肾脏、胰腺和胎盘表达最高。人类视网膜变性是一种常染色体隐性遗传病，人类Prominin-1基因1878位的单核苷酸缺失可导致蛋白质过早截断。艾尔2000)。CD133在细胞膜突起中的定位表明，CD133在细胞的极性、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发挥了作用。利用串联亲和纯化(TAP)和质谱学，我们希望确定CD133的结合伙伴，以便了解CD133下游的信号事件。

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.