title: Role of TAZ as mediator of Wnt signaling.
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.
authors.affiliation: Department of Biomedical Sciences, University of Padua School of Medicine, viale Colombo 3, 35126 Padua, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Azzolin
authors.forename: Francesca
authors.initials: F
authors.lastname: Zanconato
authors.forename: Silvia
authors.initials: S
authors.lastname: Bresolin
authors.forename: Mattia
authors.initials: M
authors.lastname: Forcato
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basso
authors.forename: Silvio
authors.initials: S
authors.lastname: Bicciato
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Cordenonsi
authors.forename: Stefano
authors.initials: S
authors.lastname: Piccolo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D051379:Mice; D059748:Proteolysis; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism; D051185:gamma Catenin / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; C551991:WWTR1 protein, human; C517794:Wwtr1 protein, mouse; D051176:beta Catenin; D051185:gamma Catenin; D038362:Glycogen Synthase Kinase 3