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 incompletely understood. Here we report that TAZ, a biologically potent transcriptional co-activator, serves as 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 are mediated by TAZ. TAZ activation is a general feature of Wnt signaling, and functionally relevant to mediate Wnt-biological effects.