Parker David S, Jemison Jemileh, Cadigan Kenneth M
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Natural Science Building, Ann Arbor 48109, USA.
Development. 2002 Jun;129(11):2565-76. doi: 10.1242/dev.129.11.2565.
The secreted glycoprotein Wingless (Wg) acts through a conserved signaling pathway to regulate target gene expression. Wg signaling causes nuclear translocation of Armadillo, the fly beta-catenin, which then complexes with the DNA-binding protein TCF, enabling it to activate transcription. Though many nuclear factors have been implicated in modulating TCF/Armadillo activity, their importance remains poorly understood. This work describes a ubiquitously expressed protein, called Pygopus, which is required for Wg signaling throughout Drosophila development. Pygopus contains a PHD finger at its C terminus, a motif often found in chromatin remodeling factors. Overexpression of pygopus also blocks the pathway, consistent with the protein acting in a complex. The pygopus mutant phenotype is highly, though not exclusively, specific for Wg signaling. Epistasis experiments indicate that Pygopus acts downstream of Armadillo nuclear import, consistent with the nuclear location of heterologously expressed protein. Our data argue strongly that Pygopus is a new core component of the Wg signaling pathway that acts downstream or at the level of TCF.
分泌型糖蛋白无翅（Wg）通过保守的信号通路来调节靶基因的表达。Wg信号传导导致果蝇β-连环蛋白犰狳的核转位，然后犰狳与DNA结合蛋白TCF形成复合物，使其能够激活转录。尽管许多核因子与调节TCF/犰狳活性有关，但其重要性仍知之甚少。这项研究描述了一种在果蝇发育过程中Wg信号传导所必需的普遍表达的蛋白质，称为Pygo。Pygo在其C末端含有一个PHD结构域，这是一种常在染色质重塑因子中发现的基序。Pygo的过表达也会阻断该信号通路，这与该蛋白在复合物中起作用一致。Pygo突变体表型虽然并非完全但高度特异性地针对Wg信号传导。上位性实验表明，Pygo在犰狳核输入的下游起作用，这与异源表达蛋白的核定位一致。我们的数据有力地表明，Pygo是Wg信号通路的一个新的核心成分，在TCF的下游或其水平上发挥作用。
