凯索/ p120连环蛋白和TCF/β-连环蛋白复合物协同调节经典Wnt基因靶点。

Kaiso/p120-catenin and TCF/beta-catenin complexes coordinately regulate canonical Wnt gene targets.

作者信息

Park Jae-Il, Kim Si Wan, Lyons Jon P, Ji Hong, Nguyen Thi T, Cho Kyucheol, Barton Michelle C, Deroo Tom, Vleminckx Kris, Moon Randall T, McCrea Pierre D

机构信息

Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.

出版信息

Dev Cell. 2005 Jun;8(6):843-54. doi: 10.1016/j.devcel.2005.04.010.

DOI:10.1016/j.devcel.2005.04.010

PMID:15935774

Abstract

Beta-catenin-dependent or canonical Wnt signals are fundamental in animal development and tumor progression. Using Xenopus laevis, we report that the BTB/POZ zinc finger family member Kaiso directly represses canonical Wnt gene targets (Siamois, c-Fos, Cyclin-D1, and c-Myc) in conjunction with TCF/LEF (TCF). Analogous to beta-catenin relief of TCF repressive activity, we show that p120-catenin relieves Kaiso-mediated repression of Siamois. Furthermore, Kaiso and TCF coassociate, and combined Kaiso and TCF derepression results in pronounced Siamois expression and increased beta-catenin coprecipitation with the Siamois promoter. The functional interdependency is underlined by Kaiso suppression of beta-catenin-induced axis duplication and by TCF-3 rescue of Kaiso depletion phenotypes. These studies point to convergence of parallel p120-catenin/Kaiso and beta-catenin/TCF signaling pathways to regulate gene expression in vertebrate development and possibly carcinogenesis.

摘要

β-连环蛋白依赖性或经典Wnt信号在动物发育和肿瘤进展中至关重要。利用非洲爪蟾，我们报道BTB/POZ锌指家族成员Kaiso与TCF/LEF（TCF）协同直接抑制经典Wnt基因靶标（Siamois、c-Fos、细胞周期蛋白D1和c-Myc）。与β-连环蛋白解除TCF抑制活性类似，我们发现p120-连环蛋白可解除Kaiso介导的对Siamois的抑制。此外，Kaiso与TCF共同结合，Kaiso和TCF联合去抑制导致Siamois明显表达，并增加β-连环蛋白与Siamois启动子的共沉淀。Kaiso对β-连环蛋白诱导的轴重复的抑制以及TCF-3对Kaiso缺失表型的挽救突出了这种功能上的相互依赖性。这些研究表明，平行的p120-连环蛋白/Kaiso和β-连环蛋白/TCF信号通路在脊椎动物发育以及可能的致癌过程中汇聚以调节基因表达。