A Novel RING Finger Protein Implicated in Neoplasia

描述(申请人提供)：杂合性缺失(LOH)和 已观察到1号染色体短臂上的细胞遗传学异常 组织学上多样的人类癌症。至少有三个不同的地区 染色体1p被认为是肿瘤抑制基因的位置。 与神经母细胞瘤和乳房的发生和/或发展有关 和结肠癌。我们已经确定了一种基因，CAR-1(与癌症相关 环-1)，精确地映射到1号染色体上的这些区域之一。我们 假设该基因是1号染色体上的肿瘤抑制基因之一 它的破坏会导致肿瘤的发生。这样做的具体目的是 研究建议是：1)获得研究CAR-1所需的工具， 包括全长cdna序列和抗体，2)筛选突变。 在CAR-1原发肿瘤样本和癌细胞系中，3)确定 CAR-1在体内外生长调节中的作用 基因特异性蛋白结构域在突变调控生长中的作用 分析，以及4)阐明CAR-1基因的细胞靶点或辅助因子 蛋白质与蛋白质相互作用的研究。因为Car-1的股票 具有一类重要基因的有趣的结构基序，其中许多 在肿瘤发生、基因的分子分析中发挥作用，如本文所述 建议将使人们更好地理解7b5和其他 与癌症进展相关的基因。

DESCRIPTION (provided by applicant): Loss of heterozygosity (LOH) and cytogenetic aberrations on the short arm of chromosome 1 have been observed in histologically diverse human cancers. At least three separate regions on chromosome 1p have been implicated as sites for tumor suppressor genes associated with the initiation and/or progression of neuroblastoma, and breast and colon carcinoma. We have identified a gene, CAR-1 (Cancer Associated RING-1), that maps exactly into one of these regions on chromosome 1. We hypothesize that this gene is one of the tumor suppressor genes on chromosome 1 p and that its disruption results in tumorigenesis. The specific aims of this research proposal are to: 1) Obtain the tools necessary to study CAR-1, including the full-length cDNA sequence and antibodies, 2) Screen for mutations in CAR-1 in primary tumor samples as well as cancer cell lines, 3) Determine the role of CAR-1 in in vitro and in vivo growth regulation and dissect the roles of the gene's specific protein domains in growth regulation by mutational analysis, and 4) Elucidate cellular targets or co-factors of the CAR-1 gene product by protein-protein interaction studies. Because CAR-1 shares interesting structural motifs with an important class of genes, many of which play roles in oncogenesis, molecular analysis of the gene as described in this proposal will lead to a better understanding of the functions of 7b5 and other related genes associated with cancer progression.