Jessen Shannon, Gu Bingnan, Dai Xing
Department of Biological Chemistry, University of California, Irvine, CA, USA.
Bioessays. 2008 May;30(5):448-56. doi: 10.1002/bies.20757.
Identification of Pygopus in Drosophila as a dedicated component of the Wg (fly homolog of mammalian Wnt) signaling cascade initiated many inquiries into the mechanism of its function. Surprisingly, the nearly exclusive role for Pygopus in Wg signal transduction in flies is not seen in mice, where Pygopus appears to have both Wnt-related and Wnt-independent functions. This review addresses the initial findings of Pygopus as a Wg/Wnt co-activator in light of recent data from both fly and mammalian studies. We compare and contrast the developmental phenotypes of pygopus mutants to those characterized for known Wg/Wnt transducers and explore the data regarding a role for mammalian Pygopus 2 in tumorigenesis. We further analyze the roles of the two conserved domains of Pygopus proteins in transcription, and propose a model for the molecular mechanism of Pygopus function in both Wg/Wnt signaling and Wnt-independent transcriptional regulation.
果蝇中Pygopus作为Wg（哺乳动物Wnt的果蝇同源物）信号级联反应的一个专门组成部分的鉴定引发了对其功能机制的诸多探究。令人惊讶的是，Pygopus在果蝇Wg信号转导中几乎唯一的作用在小鼠中并未出现，在小鼠中Pygopus似乎同时具有与Wnt相关和不依赖Wnt的功能。鉴于来自果蝇和哺乳动物研究的最新数据，本综述探讨了Pygopus作为Wg/Wnt共激活因子的初步发现。我们将pygopus突变体的发育表型与已知Wg/Wnt转导因子的发育表型进行比较和对比，并探究有关哺乳动物Pygopus 2在肿瘤发生中作用的数据。我们进一步分析了Pygopus蛋白的两个保守结构域在转录中的作用，并提出了一个关于Pygopus在Wg/Wnt信号传导和不依赖Wnt的转录调控中功能的分子机制模型。
