Wingless-independent association of pygopus with dTCF target genes
Wingless-independent association of pygopus with dTCF target genes
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DOI：
10.1016/j.cub.2007.01.063
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发表时间：
2007-03-20
期刊：
影响因子：
9.2
通讯作者：
Bienz, Mariann
中科院分区：
文献类型：
--
作者：
de la Roche, Marc;Bienz, Mariann
Wnt信号通路在动物发育过程中控制着许多细胞的命运。其不适当的活动可导致许多人体组织的癌症。经典Wnt通路的一个关键效应子是β-连环蛋白（或果蝇犰狳），一种高度不稳定的磷酸化蛋白，在细胞核和细胞质之间快速穿梭。Wnt信号传导抑制其磷酸化和降解;这允许其与结合到Wnt靶基因的TCF/LEF因子缔合，并通过募集染色质修饰和重塑因子来刺激它们的转录。Armadillo/β-连环蛋白的转录活性还取决于Pygopus（Pygo），Pygopus是一种核蛋白，其通过Legless/BCL 9衔接子与其相关联。已经提出Pygo在Writ信号传导期间通过Armadillo和Legless与TCF靶基因缔合，以通过其Nbox基序募集转录辅激活因子。在这里，我们报告Pygo与果蝇唾液腺和组织培养细胞中的dTCF靶基因组成性相关。我们的证据表明，这种关联依赖于dTCF和Pygo的Nbox基序，但不腿。因此，我们提出了一种替代模型，根据该模型，Pygo在Wnt信号传导开始时或在低信号传导水平下起作用，以在dTCF靶基因处捕获Armadillo，从而使Armadillo和dTCF之间的相互作用成为可能，从而使Armadillo介导的转录辅激活因子的募集成为可能。
The Wnt signaling pathway controls numerous cell fates during animal development. Its inappropriate activity can lead to cancer in many human tissues. A key effector of the canonical Wnt pathway is beta-catenin (or Drosophila Armadillo), a highly unstable phosphorylated protein that shuttles rapidly between nucleus and cytoplasm. Wnt signaling inhibits its phosphorylation and degradation; this allows it to associate with TCF/LEF factors bound to Wnt target genes and to stimulate their transcription by recruiting chromatin modifying and remodeling factors. The transcriptional activity of Armadillo/beta-catenin also depends on Pygopus (Pygo), a nuclear protein with which it associates through the Legless/BCL9 adaptor. It has been proposed that Pygo associates with TCF target genes during Writ signaling through Armadillo and Legless to recruit a transcriptional coactivator through its Nbox motif. Here, we report that Pygo is associated constitutively with dTCF target genes in Drosophila salivary glands and tissue-culture cells. Our evidence indicates that this association depends on dTCF and on the Nbox motif of Pygo, but not on Legless. We thus propose an alternative model according to which Pygo functions at the onset of Wnt signaling, or at low signaling levels, to capture Armadillo at dTCF target genes, thus enabling the interaction between Armadillo and dTCF and, consequently, the Armadillo-mediated recruitment of transcriptional coactivators.