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/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.

Role of TAZ as Mediator of Wnt Signaling / Azzolin, L; Zanconato, F; Bresolin, S; Forcato, Mattia; Basso, G; Bicciato, Silvio; Cordenonsi, M; Piccolo, S.. - In: CELL. - ISSN 0092-8674. - STAMPA. - 151(7):(2012), pp. 1443-1456. [10.1016/j.cell.2012.11.027]

Role of TAZ as Mediator of Wnt Signaling

FORCATO, Mattia;BICCIATO, Silvio;
2012

Abstract

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/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.
2012
151(7)
1443
1456
Role of TAZ as Mediator of Wnt Signaling / Azzolin, L; Zanconato, F; Bresolin, S; Forcato, Mattia; Basso, G; Bicciato, Silvio; Cordenonsi, M; Piccolo, S.. - In: CELL. - ISSN 0092-8674. - STAMPA. - 151(7):(2012), pp. 1443-1456. [10.1016/j.cell.2012.11.027]
Azzolin, L; Zanconato, F; Bresolin, S; Forcato, Mattia; Basso, G; Bicciato, Silvio; Cordenonsi, M; Piccolo, S.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/896689
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