β-Catenin can bind directly to CRM1 independently of adenomatous polyposis coli, which affects its nuclear localization and LEF-1/β-catenin-dependent gene expression
β-Catenin can bind directly to CRM1 independently of adenomatous polyposis coli, which affects its nuclear localization and LEF-1/β-catenin-dependent gene expression
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DOI：
10.1016/j.cellbi.2007.12.008
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发表时间：
2008-04-01
影响因子：
3.9
通讯作者：
Kim, Kwonseop
中科院分区：
文献类型：
--
作者：
Ki, Hyunkyoung;Oh, Minsoo;Kim, Kwonseop
核β-连环蛋白影响肿瘤的发育过程和进展。然而，β-连环蛋白核输出的精确机制尚不完全清楚。我们发现β-连环蛋白可以通过其中央犰狳（ARM）重复区域直接与CRM1结合，独立于腺瘤性结肠息肉病（APC）蛋白。 CRM1 过表达将核 β-连环蛋白转运到细胞质中，并降低 LEF-1/β-连环蛋白依赖性转录活性，这也受到 E-钙粘蛋白共过表达的影响。 CRM1 与 E-钙粘蛋白和 LEF-1 竞争与 β-连环蛋白的结合。 β-连环蛋白可以通过其氨基酸 342 和 350 之间的必需序列直接与 APC 相互作用。定点 β-连环蛋白突变体 (NES2(-)) 可以与 CRM1 相互作用，但不能与 APC 相互作用，仍然保留其从细胞核输出的能力及其反式激活活性。这表明 CRM1 可以独立于 APC 作为 β-连环蛋白的有效核输出蛋白。这些结果强烈表明 CRM1 介导的途径参与细胞核中核 β-连环蛋白的有效转运。 (C) 2008 年国际细胞生物学联合会。由爱思唯尔有限公司出版。保留所有权利。
Nuclear beta-catenin affects the developmental process and progression of tumors. However, the precise mechanism for the nuclear export of beta-catenin is not completely understood. We found that beta-catenin can bind directly to CRM1 through its central armadillo ( ARM) repeats region, independently of the adenomatous polyposis coli ( APC) protein. CRM1 overexpression transports nuclear beta-catenin into the cytoplasm and decreases LEF-1/beta-catenin-dependent transcriptional activity, which is also affected by the co-overexpression of E-cadherin. CRM1 competed with E-cadherin and LEF-1 for binding to beta-catenin. beta-catenin could interact directly with APC through its essential sequences between amino acids 342 and 350. The site-directed beta-catenin mutant (NES2(-)), which could interact with CRM1, but not with APC, still retained its ability to export from the nucleus and its transactivational activity. This suggests that CRM1 can function as an efficient nuclear exporter for beta-catenin independently of APC. These results strongly suggest that the CRM1-mediated pathway is involved in the efficient transport of nuclear beta-catenin in the nucleus of cells. (C) 2008 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.