A Wnt survival guide: from flies to human disease.
A Wnt survival guide: from flies to human disease.
复制标题
DOI：
10.1038/jid.2008.445
复制
发表时间：
2009-07
期刊：
影响因子：
--
通讯作者：
Moon RT
中科院分区：
文献类型：
--
作者：
Chien AJ;Conrad WH;Moon RT
自从研究人员发现果蝇无翅（Wg）基因和脊椎动物致癌基因int-1之间的联系，从而建立了称为Wnts的信号蛋白家族以来，已经过去了二十年。自Wnt信号转导领域成立以来，已经在人类中鉴定出19种Wnt亚型。这些分泌的糖蛋白可以激活脊椎动物细胞中至少两种不同的信号传导途径，导致调节大量生物过程的细胞变化，包括胚胎发育、细胞命运、细胞增殖、细胞迁移、干细胞维持、肿瘤抑制和肿瘤发生。在某些情况下，Wnt同种型的一个子集激活典型的Wnt/β-连环蛋白途径，其特征在于响应于Wnt配体与其同源受体的结合而激活某些β-连环蛋白应答性靶基因。同样，在某些细胞环境中，Wnt亚型的第二个子集激活β-连环蛋白非依赖性途径，包括Wnt/钙（Wnt/Ca）途径和Wnt/平面细胞极性（Wnt/PCP）途径。此外，研究已经确定了几种已知调节Wnt信号传导的分泌蛋白，包括Dickkopf（DKK）家族、分泌卷曲相关蛋白（sFRPs）和Wnt抑制因子-1（WIF-1）。能够提供全基因组表达数据的技术的出现继续涉及Wnt和在越来越多的疾病过程中调节Wnt信号通路的蛋白质。这篇综述的目的是提供一个关于Wnt领域的背景，这将有助于在人类疾病的背景下解释和研究Wnt信号。
It has been two decades since investigators discovered the link between the Drosophila wingless (Wg) gene and the vertebrate oncogene int-1, thus establishing the family of signaling proteins known as Wnts. Since the inception of the Wnt signaling field, there have been 19 Wnt isoforms identified in humans. These secreted glycoproteins can activate at least two distinct signaling pathways in vertebrate cells, leading to cellular changes that regulate a vast array of biological processes, including embryonic development, cell fate, cell proliferation, cell migration, stem cell maintenance, tumor suppression, and oncogenesis. In certain contexts, one subset of Wnt isoforms activates the canonical Wnt/β-catenin pathway that is characterized by the activation of certain β-catenin-responsive target genes in response to the binding of Wnt ligand to its cognate receptors. Similarly, a second subset of Wnt isoforms activates β-catenin-independent pathways, including the Wnt/ calcium (Wnt/Ca) pathway and the Wnt/planar cell polarity (Wnt/PCP) pathway, in certain cellular contexts. In addition, research has identified several secreted proteins known to regulate Wnt signaling, including the Dickkopf (DKK) family, secreted Frizzled-related proteins (sFRPs), and Wnt inhibitory factor-1 (WIF-1). The advent of technologies that can provide genome-wide expression data continues to implicate Wnts and proteins that regulate Wnt signaling pathways in a growing number of disease processes. The aim of this review is to provide a context on the Wnt field that will facilitate the interpretation and study of Wnt signaling in the context of human disease.