Wnt/Wingless signaling requires BCL9/legless-mediated recruitment of pygopus to the nuclear β-catenin-TCF complex
Wnt/Wingless signaling requires BCL9/legless-mediated recruitment of pygopus to the nuclear β-catenin-TCF complex
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DOI：
10.1016/s0092-8674(02)00679-7
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发表时间：
2002-04-05
期刊：
影响因子：
64.5
通讯作者：
Basler, K
中科院分区：
文献类型：
--
作者：
Kramps, T;Peter, O;Basler, K
WNT/Wingless信号控制着动物发育过程中的许多基本过程。WNT的转导是通过β-连环蛋白与核TCFDNA结合因子的结合来介导的。在这里，我们报道了果蝇中两个片段的极性基因，无腿(Lgs)和吡戈鸟(Pygopus)，我们证明了它们的产物是在核β-连环素水平上进行Wnt信号转导所必需的。LGS编码人类BCL9的同系物，我们提供了遗传和分子证据，证明这些蛋白通过物理上将PYGO与β-连环蛋白联系起来发挥功能。我们的结果表明，PYGO的招募允许β-连环素转录激活WNT靶基因，并增加了这些事件的解除调控可能在B细胞恶性肿瘤的发展中起因果作用的可能性。
Wnt/Wingless signaling controls many fundamental processes during animal development. Wnt transduction is mediated by the association of beta-catenin with nuclear TCF DNA binding factors. Here we report the identification of two segment polarity genes in Drosophila, legless (lgs), and pygopus (pygo), and we show that their products are required for Wnt signal transduction at the level of nuclear beta-catenin. Lgs encodes the homolog of human BCL9, and we provide genetic and molecular evidence that these proteins exert their function by physically linking Pygo to beta-catenin. Our results suggest that the recruitment of Pygo permits beta-catenin to transcriptionally activate Wnt target genes and raise the possibility that a deregulation of these events may play a causal role in the development of B cell malignancies.