Kaiso/p120-catenin and TCF/β-catenin complexes coordinately regulate canonical Wnt gene targets
Kaiso/p120-catenin and TCF/β-catenin complexes coordinately regulate canonical Wnt gene targets
复制标题
Kaiso/p120-连环蛋白和 TCF/β-连环蛋白复合物协调调节经典 Wnt 基因靶标
DOI：
10.1016/j.devcel.2005.04.010
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发表时间：
2005-06-01
影响因子：
11.8
通讯作者：
McCrea, PD
中科院分区：
文献类型：
--
作者：
Park, JI;Kim, SW;McCrea, PD
β-连环蛋白依赖或规范的WRIT信号在动物发育和肿瘤进展中是基本的。利用非洲爪哇，我们报道了BTB/POZ锌指家族成员K还与Tcf/Lef(Tcf)一起直接抑制规范的WRIT基因靶标(siamois、c-Fos、Cyclin-D1和c-Myc)。类似于P-连环蛋白对TCF抑制活性的解除，我们发现p120-连环蛋白可以解除Kaiso介导的对SIAMOIS的抑制。此外，KAlso和Tcf共同作用，以及Kaiso和Tcf联合去抑制导致显著的siamois表达，并增加β-catenin与siamois启动子的共沉淀。KAlso抑制P-连环蛋白诱导的轴复制和TCF-3对KAlso耗竭表型的挽救强调了功能的相互依赖。这些研究指出，在脊椎动物发育和可能的癌症发生中，并行的p120-连环素/Kaiso和β-连环素/TCF信号通路趋同，以调节基因表达。
beta-catenin-dependent or canonical Writ signals are fundamental in animal development and tumor progression. Using Xenopus laevis, we report that the BTB/POZ zinc finger family member Kalso directly represses canonical Writ gene targets (Siamois, c-Fos, Cyclin-D1, and c-Myc) in conjunction with TCF/LEF (TCF). Analogous to P-catenin relief of TCF repressive activity, we show that p120-catenin relieves Kaiso-mediated repression of Siamois. Furthermore, Kalso 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 Kalso suppression of P-catenin-induced axis duplication and by TCF-3 rescue of Kalso 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.