Role of TAZ as mediator of Wnt signaling

Cell. 2012 Dec 21;151(7):1443-56. doi: 10.1016/j.cell.2012.11.027. Epub 2012 Dec 13.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cell Line
  • Cell Line, Tumor
  • Glycogen Synthase Kinase 3 / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Proteolysis
  • Transcription Factors
  • Wnt Signaling Pathway*
  • beta Catenin / metabolism
  • gamma Catenin / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Intracellular Signaling Peptides and Proteins
  • Transcription Factors
  • WWTR1 protein, human
  • Wwtr1 protein, mouse
  • beta Catenin
  • gamma Catenin
  • Glycogen Synthase Kinase 3

Associated data

  • GEO/GSE39907