Role of TAZ as Mediator of Wnt Signaling

SummaryWnt 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/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.

Graphical AbstractFigure optionsDownload high-quality image (330 K)Download as PowerPoint slideHighlights
► Wnt signals through TAZ, in parallel to β-catenin
► TAZ is a component of the Wnt signaling cascade and mediates Wnt biological response
► In the absence of Wnt, β-catenin mediates TAZ degradation
► Wnt regulation of TAZ stability is independent of the Hippo pathway