Program in Cell and Molecular Biology, University of Michigan, Ann Arbor, 48109-1048, USA.
Acta Physiol (Oxf). 2012 Jan;204(1):74-109. doi: 10.1111/j.1748-1716.2011.02293.x. Epub 2011 May 27.
Wnt/β-catenin signalling is known to play many roles in metazoan development and tissue homeostasis. Misregulation of the pathway has also been linked to many human diseases. In this review, specific aspects of the pathway's involvement in these processes are discussed, with an emphasis on how Wnt/β-catenin signalling regulates gene expression in a cell and temporally specific manner. The T-cell factor (TCF) family of transcription factors, which mediate a large portion of Wnt/β-catenin signalling, will be discussed in detail. Invertebrates contain a single TCF gene that contains two DNA-binding domains, the high mobility group (HMG) domain and the C-clamp, which increases the specificity of DNA binding. In vertebrates, the situation is more complex, with four TCF genes producing many isoforms that contain the HMG domain, but only some of which possess a C-clamp. Vertebrate TCFs have been reported to act in concert with many other transcription factors, which may explain how they obtain sufficient specificity for specific DNA sequences, as well as how they achieve a wide diversity of transcriptional outputs in different cells.
Wnt/β-catenin 信号通路在后生动物发育和组织稳态中发挥着多种作用。该通路的失调也与许多人类疾病有关。在这篇综述中,我们将讨论该通路在这些过程中的特定作用,重点讨论 Wnt/β-catenin 信号通路如何以细胞和时间特异性的方式调节基因表达。我们将详细讨论 T 细胞因子(TCF)家族转录因子,它们介导了 Wnt/β-catenin 信号通路的很大一部分。无脊椎动物只含有一个 TCF 基因,该基因包含两个 DNA 结合域,即高迁移率族(HMG)结构域和 C 夹,这增加了 DNA 结合的特异性。在脊椎动物中,情况更为复杂,有四个 TCF 基因产生许多包含 HMG 结构域的同工型,但只有其中一些具有 C 夹。已经报道脊椎动物 TCF 与许多其他转录因子协同作用,这可能解释了它们如何获得特定 DNA 序列的足够特异性,以及它们如何在不同细胞中实现广泛的转录输出多样性。