科学家揭示Wnt信号中的重要因子

Wnt生长因子是决定细胞命运的基本调节因子，但是Wnt信号是如何在生物反应中转录翻译的目前还了解不太*。近日来自意大利帕多瓦大学医学院的科研人员报导了作为下游元件的信号/β-连环蛋白级联中一个强大的生物转录激活TAZ，这扩宽了人们对Wnt信号通路的认识，相关论文发表在2012年12月13日的Cell杂志上。

TAZ基因编码的蛋白质在心脏和骨骼肌中表达水平很高，这个基因的突变已与一些临床疾病存在关联。在本次研究中，研究人员发现TAZ在Hippo信号通路中充分发挥了介质作用，在没有Wnt 信号的条件下，作为β-catenin的复合体组成部分的APC, Axin, 和 GSK3保持较低水平，TAZ降解取决于磷酸化β-连环（TAZ及其泛素连接酶β- trcp）。

在Wnt 信号中，β-catenin复合体的破坏导致TAZ降解。全基因组水平上，很大一部分的Wnt 基因转录的反应由TAZ.介导。TAZ.的激活是Wnt信号和相关生物效应中的普遍特征。

原文摘要：

Role of TAZ as Mediator of Wnt Signaling

Wnt growth factors are fundamental regulators of cell fate, but how the Wnt signal is translated into biological responses is incompley understood. Here, we report that TAZ, a biologically potent transcriptional coactivator, serves as a downstream element of the Wnt/β-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 β-catenin destruction complex—APC, Axin, and GSK3—are also required to keep TAZ at low levels. TAZ degradation depends on phosphorylated β-catenin that bridges TAZ to its ubiquitin ligase β-TrCP. Upon Wnt signaling, escape of β-catenin from the destruction complex impairs TAZ degradation and leads to concomitant accumulation of β-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.