Role of TAZ as Mediator of Wnt Signaling
Role of TAZ as Mediator of Wnt Signaling
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DOI：
10.1016/j.cell.2012.11.027
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发表时间：
2012-12-21
期刊：
影响因子：
64.5
通讯作者：
Piccolo, Stefano
中科院分区：
文献类型：
--
作者：
Azzolin, Luca;Zanconato, Francesca;Piccolo, Stefano
Wnt生长因子是细胞命运的基本调节因子，但Wnt信号如何转化为生物反应尚不完全清楚。在这里，我们报道了TAZ，一种生物学上有效的转录辅激活因子，作为Wnt/ β -连环蛋白级联的下游元件。TAZ的这种功能独立于它作为Hippo信号传导介质的作用。在缺乏Wnt活性的情况下，β -连环蛋白破坏复合物的组分——apc、Axin和gsk3也需要保持TAZ在低水平。TAZ的降解依赖于磷酸化的-连环蛋白，该蛋白将TAZ与其泛素连接酶- trcp连接起来。在Wnt信号传导过程中，β -连环蛋白从破坏复合体中逃逸，损害了TAZ的降解，并导致β -连环蛋白和TAZ的累积。在全基因组水平上，TAZ介导了Wnt转录反应的很大一部分。TAZ激活是Wnt信号的普遍特征，在功能上与介导Wnt生物学效应相关。
Wnt growth factors are fundamental regulators of cell fate, but how the Wnt signal is translated into biological responses is incompletely understood. Here, we report that TAZ, a biologically potent transcriptional coactivator, serves as a downstream element of the Wnt/beta-catenin cascade. This function of TAZ is independent from its well-established role as mediator of Hippo signaling. In the absence of Wnt activity, the components of the beta-catenin destruction complex-APC, Axin, and GSK3-are also required to keep TAZ at low levels. TAZ degradation depends on phosphorylated beta-catenin that bridges TAZ to its ubiquitin ligase beta-TrCP. Upon Wnt signaling, escape of beta-catenin from the destruction complex impairs TAZ degradation and leads to concomitant accumulation of beta-catenin and TAZ. At the genome-wide level, a substantial portion of Wnt transcriptional responses is mediated by TAZ. TAZ activation is a general feature of Wnt signaling and is functionally relevant to mediate Wnt biological effects.