Expression and Function of EPLIN

EPLIN的表达及功能

• 批准号: 6438889
• 负责人: David D. Chang
• 金额: $ 33.99万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-10 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6438889
• 关键词: SCID mouse; actins; carcinogenesis; cytoskeletal proteins; developmental genetics; embryogenesis; gene expression; gene targeting; genetically modified animals; homeostasis; neoplasm /cancer genetics; prostate; prostate neoplasms; protein structure function

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.

描述：（由申请人提供）EPLIN是一种基因， 在癌细胞中下调。它编码一种新的LIM结构域蛋白， 与细胞骨架结构共定位。有两种已知的异构体 EPLIN（α和β），通过来自一个细胞的替代启动子使用产生。 位于染色体12 q13的单拷贝基因。EPLIN的表达是 在许多上皮癌细胞中发生了改变，包括几种前列腺癌细胞， 癌细胞系、异种移植物和肿瘤。EPLIN的过表达可以改变 肌动蛋白纤维在细胞中，并抑制NIH 3 T3的锚定非依赖性生长 Cdc 42或EWS/Fli-1转化的细胞。纯化的EPLIN可以结合丝状 肌动蛋白和改变肌动蛋白聚合在体外。EPLIN的精确功能 EPLIN表达与转化的关系尚不清楚。 然而，EPLIN的已知特征表明， 细胞凋亡相关蛋白可能在调节细胞凋亡中起作用。 细胞骨架我们认为EPLIN的功能是调节 通过将肌动蛋白丝连接到细胞中的其他结构或 调节蛋白因此，EPLIN的中断将改变 细胞结构和损害细胞-细胞和/或细胞-基质相互作用。我们 假设EPLIN的异常可能在 通过破坏上皮腺体的组织来阻止癌症的进展， 促进细胞迁移。这笔赠款的具体目标将检验我们的想法 通过研究（i）EPLIN的生化特性;（ii）EPLIN在 正常和癌细胞;（iii）EPLIN在胚胎发生过程中的功能， 组织内稳态

项目成果

Pseudoaneuploid subpopulations detected in normal upper aerodigestive tract mucosa consistent with physiological apoptosis in normally differentiating squamous mucosa.

在正常上呼吸消化道粘膜中检测到的假非整倍体亚群与正常分化的鳞状粘膜中的生理性细胞凋亡一致。

• DOI: 10.1016/j.otohns.2004.04.036
• 发表时间: 2004
• 期刊: Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.
• 作者: El-Rayes,BassilF;Korkmaz,Hakan;Maciorowski,Zosia;Sakr,Wael;Jacobs,JohnR;Ensley,JohnF
• 通讯作者: Ensley,JohnF

EPLIN regulates actin dynamics by cross-linking and stabilizing filaments.

Eplin通过交联和稳定细丝来调节肌动蛋白动力学。

• DOI: 10.1083/jcb.200212057
• 发表时间: 2003-02-03
• 期刊: JOURNAL OF CELL BIOLOGY
• 影响因子: 7.8
• 作者: Maul, Raymond S;Song, Yuhong;Amann, Kurt J;Gerbin, Sachi C;Pollard, Thomas D;Chang, David D
• 通讯作者: Chang, David D