Wnt signaling is an evolutionarily conserved metazoan cell communication pathway required for proper animal development. Of the myriad of signaling events that have been ascribed to cellular activation by Wnt ligands, the canonical Wnt/β-catenin pathway has been the most studied and best understood. Misregulation of Wnt/β-catenin signaling has been implicated in developmental defects in the embryo and major diseases in the adult. Despite the latter, no drugs that inhibit the Wnt/β-catenin pathway have been approved by the FDA. In this review, we explore the least understood step in the Wnt/β-catenin pathway—nuclear regulation of Wnt target gene transcription. We initially describe our current understanding of the importation of β-catenin into the nucleus. We then focus on the mechanism of action of the major nuclear proteins implicated in driving gene transcription. Finally, we explore the concept of a nuclear Wnt enhanceosome and propose a modified model that describes the necessary components for the transcription of Wnt target genes.

中文翻译：

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Wnt/β-连环蛋白信号的核调节：这是一个复杂的情况

Wnt 信号是一种进化上保守的后生动物细胞通讯通路，是动物正常发育所必需的。在归因于 Wnt 配体细胞激活的无数信号转导事件中，经典的 Wnt/β-连环蛋白通路是研究最多和理解得最好的。Wnt/β-连环蛋白信号通路的失调与胚胎发育缺陷和成人主要疾病有关。尽管存在后者，但 FDA 尚未批准任何抑制 Wnt/β-catenin 通路的药物。在这篇综述中，我们探索了 Wnt/β-连环蛋白通路中了解最少的步骤——Wnt 靶基因转录的核调控。我们首先描述了我们目前对将 β-连环蛋白输入细胞核的理解。然后我们关注与驱动基因转录有关的主要核蛋白的作用机制。最后，我们探讨了核 Wnt 增强体的概念，并提出了一种改进的模型，该模型描述了 Wnt 靶基因转录的必要成分。