&bgr;-catenin转录复合体的环境依赖性调控支持Wnt/&bgr;-catenin信号传导的多种功能

Takamasa Masuda, T. Ishitani
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引用次数: 28

摘要

Wnt/ -catenin信号在动物的一生中被反复激活,它通过其基本的核效应物-catenin控制基因表达,调节胚胎发生、器官发生和成体体内平衡。虽然&bgr;-catenin转录复合体有能力诱导许多基因的表达来发挥其不同的作用,但它会根据环境从众多靶基因中选择并激活特定的一组基因。例如,&bgr;-catenin转录复合体在神经祖细胞中刺激细胞周期相关基因的表达和细胞增殖,同时在分化神经元中促进神经分化相关基因的表达。最近使用动物和细胞培养模型的研究逐渐提高了我们对&bgr;-catenin转录复合物的上下文依赖作用的分子基础的理解。在这里,我们描述了支持&bgr;-catenin介导的环境依赖基因调控的八种机制,以及它们在脊椎动物发育过程中的时空调控。此外,我们还讨论了它们对Wnt/&bgr;-catenin信号传导的各种功能的贡献。
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Context-dependent regulation of the &bgr;-catenin transcriptional complex supports diverse functions of Wnt/&bgr;-catenin signaling
Wnt/&bgr;-catenin signaling is activated repeatedly during an animal’s lifespan, and it controls gene expression through its essential nuclear effector, &bgr;-catenin, to regulate embryogenesis, organogenesis, and adult homeostasis. Although the &bgr;-catenin transcriptional complex has the ability to induce the expression of many genes to exert its diverse roles, it chooses and transactivates a specific gene set from among its numerous target genes depending on the context. For example, the &bgr;-catenin transcriptional complex stimulates the expression of cell cycle-related genes and consequent cell proliferation in neural progenitor cells, while it promotes the expression of neural differentiation-related genes in differentiating neurons. Recent studies using animal and cell culture models have gradually improved our understanding of the molecular basis underlying such context-dependent actions of the &bgr;-catenin transcriptional complex. Here, we describe eight mechanisms that support &bgr;-catenin-mediated context-dependent gene regulation, and their spatio-temporal regulation during vertebrate development. In addition, we discuss their contribution to the diverse functions of Wnt/&bgr;-catenin signaling.
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