Expression and Function of EPLIN

描述：(申请人提供)EPLIN是一种转录水平的基因 在癌细胞中表达下调。它编码一种新的LIM结构域蛋白，该蛋白 与细胞骨架结构共定位。已知的亚型有两种 EPLIN(阿尔法和贝塔)，由替代启动子用法从 单拷贝基因位于染色体12q13。Eplin的表达为 在一些上皮癌细胞中发生改变，包括几个前列腺癌 癌细胞系、异种移植和肿瘤。EPLIN的过度表达可能会改变 细胞内的肌动蛋白纤维和抑制NIH3T3细胞的锚定非依赖性生长 Cdc42或EWS/Fli-1转化的细胞。纯化的EPLIN可以结合丝状结构 肌动蛋白和改变肌动蛋白的体外聚合。EPLIN的精确功能 Eplin的表达与转化之间的关系尚不清楚。 然而，EPLIN的已知特征表明，这 细胞骨架相关蛋白可能在细胞周期调控中发挥作用 细胞骨架。我们认为Eplin具有调节肌动蛋白的功能 通过将肌动蛋白细丝连接到其他结构或 调节蛋白。因此，EPLIN的中断将改变 并损害细胞与细胞和/或细胞与基质的相互作用。我们 假设EPLIN中的异常可能在 通过扰乱上皮腺和上皮腺的组织来进展癌症 促进细胞迁移。这笔赠款的具体目的将检验我们的想法 通过研究(I)EPLIN的生化性质；(II)EPLIN在体内的作用 正常细胞和癌细胞；(Iii)Eplin在胚胎发生和发育过程中的作用 组织动态平衡。

DESCRIPTION: (provided by applicant) EPLIN is a gene that is transcriptionally downregulated in cancer cells. It encodes a novel LIM domain protein that co-localizes with the cytoskeletal structures. There are two known isoforms of EPLIN (alpha and beta), generated by an alternative promoter usage from a single copy gene located in chromosome 12q13. The expression of EPLIN is altered in a number of epithelial cancer cells, including several prostate cancer cell lines, xenografts, and tumors. Overexpression of EPLIN can alter actin fibers in the cell and inhibit anchorage independent growth of NIH3T3 cells transformed by Cdc42 or EWS/Fli-1. Purified EPLIN can bind filamentous actin and alter actin polymerization in vitro. The precise function of EPLIN and the relationship between EPLIN expression and transformation are not known. However, the known characteristics of EPLIN suggest that this cytoskeleton-associated protein may play a role in the regulation of the cytoskeleton. We believe that EPLIN functions to regulate the actin cytoskeleton in the cell by linking actin filaments to other structural or regulatory proteins. The disruption of EPLIN would therefore alter cytoarchitecture and impair cell-cell and/or cell-matrix interaction. We postulate that abnormalities in EPLIN could potentially play a role during progression of cancer by disrupting the organization of epithelial glands and promoting cell migration. The specific aims of this grant will test our ideas by studying (i) biochemical properties of EPLIN; (ii) function of EPLIN in normal and cancer cells; (iii) function of EPLIN during embryogenesis and in tissue homeostasis.