The armadillo repeat domain of the APC tumor suppressor protein interacts with Striatin family members
The armadillo repeat domain of the APC tumor suppressor protein interacts with Striatin family members
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DOI：
10.1016/j.bbamcr.2008.04.017
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发表时间：
2008-10-01
影响因子：
5.1
通讯作者：
Rosin-Arbesfeld, Rina
中科院分区：
文献类型：
--
作者：
Breitman, Maya;Zilberberg, Alona;Rosin-Arbesfeld, Rina
大肠腺瘤性息肉病（APC）是一种多功能的肿瘤抑制蛋白，负调控Wnt信号通路。APC基因在各种组织中普遍表达，特别是在整个大肠和中枢神经系统中。编码APC的基因突变已在大多数结直肠癌和其他类型的癌症中发现。APC基因产物是一种大的多结构域蛋白，其与多种蛋白质相互作用，其中许多蛋白质与APC的高度保守的Armadillo重复结构域结合。通过其结合伴侣，APC影响大量重要的细胞过程，包括细胞-细胞粘附、细胞迁移、肌动蛋白和微管细胞骨架的组织、纺锤体形成和染色体分离。控制这些不同APC功能的分子机制仅部分了解。在这里，我们描述了一个额外的APC犰狳重复结合伙伴的识别-纹状体蛋白。Striatin家族成员是主要是神经元的多结构域分子，被认为起支架作用。我们发现Striatin在上皮细胞中表达，并与APC共定位于上皮紧密连接区室和PC 12细胞的神经突尖端。APC和Striatin的连接定位是肌动蛋白依赖性的。APC或Striatin的耗竭影响紧密连接蛋白ZO-1的定位并改变F-肌动蛋白的组织。这些结果提高了APC对细胞-细胞粘附的贡献可能是通过与上皮细胞紧密连接区室中的Striatin相互作用的可能性。(c)2008 Elsevier B. V.保留所有权利。
Adenomatous polyposis coli (APC) is a multifunctional tumor suppressor protein that negatively regulates the Wnt signaling pathway. The APC gene is ubiquitously expressed in various tissues, especially throughout the large intestine and central nervous system. Mutations in the gene encoding APC have been found in most colorectal cancers and in other types of cancer. The APC gene product is a large multidomain protein that interacts with a variety of proteins, many of which bind to the well conserved armadillo repeat domain of APC. Through its binding partners, APC affects a large number of important cellular processes, including cell-cell adhesion, cell migration, organization of the actin and microtubule cytoskeletons, spindle formation and chromosome segregation. The molecular mechanisms that control these diverse APC functions are only partly understood. Here we describe the identification of an additional APC armadillo repeat binding partner - the Striatin protein. The Striatin family members are multidomain molecules that are mainly neuronal and are thought to function as scaffolds. We have found that Striatin is expressed in epithelial cells and co-localizes with APC in the epithelial tight junction compartment and in neurite tips of PC12 cells. The junctional localization of APC and Striatin is actin-dependent. Depletion of APC or Striatin affected the localization of the tight junction protein ZO-1 and altered the organization of F-actin. These results raise the possibility that the contribution of APC to cell-cell adhesion may be through interaction with Striatin in the tight junction compartment of epithelial cells. (c) 2008 Elsevier B.V. All rights reserved.